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1. Multi-Institutional Evaluation of Pathologists Assessment Compared to Immunoscore.

Author

Willis, Joseph, Anders, Robert, Torigoe, Toshihiko, Hirohashi, Yoshihiko, Bifulco, Carlo, Zlobec, Inti, Mlecnik, Bernhard, Demaria, Sandra, Choi, Won-Tak, Dundr, Pavel, Tatangelo, Fabiana, Di Mauro, Annabella, Baldin, Pamela, Bindea, Gabriela, Marliot, Florence, Haicheur, Nacilla, Fredriksen, Tessa, Kirilovsky, Amos, Buttard, Bénédicte, Vasaturo, Angela, Lafontaine, Lucie, Maby, Pauline, El Sissy, Carine, Hijazi, Assia, Majdi, Amine, Lagorce, Christine, Berger, Anne, Van den Eynde, Marc, Pagès, Franck, Lugli, Alessandro, and Galon, Jérôme

Subjects
T cell, anatomopathology, colon cancer, digital pathology, immunoscore, prognostic markers, risk stratification, tumor microenvironment
Abstract

BACKGROUND: The Immunoscore (IS) is a quantitative digital pathology assay that evaluates the immune response in cancer patients. This study reports on the reproducibility of pathologists visual assessment of CD3+- and CD8+-stained colon tumors, compared to IS quantification. METHODS: An international group of expert pathologists evaluated 540 images from 270 randomly selected colon cancer (CC) cases. Concordance between pathologists T-score, corresponding hematoxylin-eosin (H&E) slides, and the digital IS was evaluated for two- and three-category IS. RESULTS: Non-concordant T-scores were reported in more than 92% of cases. Disagreement between semi-quantitative visual assessment of T-score and the reference IS was observed in 91% and 96% of cases before and after training, respectively. Statistical analyses showed that the concordance index between pathologists and the digital IS was weak in two- and three-category IS, respectively. After training, 42% of cases had a change in T-score, but no improvement was observed with a Kappa of 0.465 and 0.374. For the 20% of patients around the cut points, no concordance was observed between pathologists and digital pathology analysis in both two- and three-category IS, before or after training (all Kappa < 0.12). CONCLUSIONS: The standardized IS assay outperformed expert pathologists T-score evaluation in the clinical setting. This study demonstrates that digital pathology, in particular digital IS, represents a novel generation of immune pathology tools for reproducible and quantitative assessment of tumor-infiltrated immune cell subtypes.

Published
2023

2. Supplementary Figure from An Autologous Dendritic Cell Vaccine Promotes Anticancer Immunity in Patients with Ovarian Cancer with Low Mutational Burden and Cold Tumors

Author

Fucikova, Jitka, primary, Hensler, Michal, primary, Kasikova, Lenka, primary, Lanickova, Tereza, primary, Pasulka, Josef, primary, Rakova, Jana, primary, Drozenova, Jana, primary, Fredriksen, Tessa, primary, Hraska, Marek, primary, Hrnciarova, Tereza, primary, Sochorova, Klara, primary, Rozkova, Daniela, primary, Sojka, Ludek, primary, Dundr, Pavel, primary, Laco, Jan, primary, Brtnicky, Tomas, primary, Praznovec, Ivan, primary, Halaska, Michael J., primary, Rob, Lukas, primary, Ryska, Ales, primary, Coosemans, An, primary, Vergote, Ignace, primary, Cibula, David, primary, Bartunkova, Jirina, primary, Galon, Jérôme, primary, Galluzzi, Lorenzo, primary, and Spisek, Radek, primary

Published
2023
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3. Supplementary Figures from A Diagnostic Biopsy-Adapted Immunoscore Predicts Response to Neoadjuvant Treatment and Selects Patients with Rectal Cancer Eligible for a Watch-and-Wait Strategy

Author

El Sissy, Carine, primary, Kirilovsky, Amos, primary, Van den Eynde, Marc, primary, Muşină, Ana-Maria, primary, Anitei, Maria-Gabriela, primary, Romero, Alfredo, primary, Marliot, Florence, primary, Junca, Audelaure, primary, Doyen, Jérôme, primary, Mlecnik, Bernhard, primary, Haicheur, Nacilla, primary, Fredriksen, Tessa, primary, Lagorce, Christine, primary, Jouret-Mourin, Anne, primary, Leonard, Daniel, primary, Bibeau, Frédéric, primary, Iseas, Soledad, primary, Roca, Enrique L., primary, Cabanne, Ana M., primary, Vaccaro, Carlos A., primary, Santino, Juan P., primary, Huertas, Eduardo, primary, Tougeron, David, primary, Carvalho, Carlos, primary, Figueiredo, Nuno, primary, Perez, Rodrigo O., primary, Habr-Gama, Angelita, primary, Scripcariu, Viorel, primary, Gerard, Jean-Pierre, primary, Galon, Jérôme, primary, Zeitoun, Guy, primary, and Pagès, Franck, primary

Published
2023
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4. Supplementary Tables from A Diagnostic Biopsy-Adapted Immunoscore Predicts Response to Neoadjuvant Treatment and Selects Patients with Rectal Cancer Eligible for a Watch-and-Wait Strategy

Author

El Sissy, Carine, primary, Kirilovsky, Amos, primary, Van den Eynde, Marc, primary, Muşină, Ana-Maria, primary, Anitei, Maria-Gabriela, primary, Romero, Alfredo, primary, Marliot, Florence, primary, Junca, Audelaure, primary, Doyen, Jérôme, primary, Mlecnik, Bernhard, primary, Haicheur, Nacilla, primary, Fredriksen, Tessa, primary, Lagorce, Christine, primary, Jouret-Mourin, Anne, primary, Leonard, Daniel, primary, Bibeau, Frédéric, primary, Iseas, Soledad, primary, Roca, Enrique L., primary, Cabanne, Ana M., primary, Vaccaro, Carlos A., primary, Santino, Juan P., primary, Huertas, Eduardo, primary, Tougeron, David, primary, Carvalho, Carlos, primary, Figueiredo, Nuno, primary, Perez, Rodrigo O., primary, Habr-Gama, Angelita, primary, Scripcariu, Viorel, primary, Gerard, Jean-Pierre, primary, Galon, Jérôme, primary, Zeitoun, Guy, primary, and Pagès, Franck, primary

Published
2023
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5. Supplementary Figure 1 from Correlation between Density of CD8+ T-cell Infiltrate in Microsatellite Unstable Colorectal Cancers and Frameshift Mutations: A Rationale for Personalized Immunotherapy

Author

Maby, Pauline, primary, Tougeron, David, primary, Hamieh, Mohamad, primary, Mlecnik, Bernhard, primary, Kora, Hafid, primary, Bindea, Gabriela, primary, Angell, Helen K., primary, Fredriksen, Tessa, primary, Elie, Nicolas, primary, Fauquembergue, Emilie, primary, Drouet, Aurélie, primary, Leprince, Jérôme, primary, Benichou, Jacques, primary, Mauillon, Jacques, primary, Le Pessot, Florence, primary, Sesboüé, Richard, primary, Tuech, Jean-Jacques, primary, Sabourin, Jean-Christophe, primary, Michel, Pierre, primary, Frébourg, Thierry, primary, Galon, Jérôme, primary, and Latouche, Jean-Baptiste, primary

Published
2023
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6. Supplementary Figure 2 from Correlation between Density of CD8+ T-cell Infiltrate in Microsatellite Unstable Colorectal Cancers and Frameshift Mutations: A Rationale for Personalized Immunotherapy

Author

Maby, Pauline, primary, Tougeron, David, primary, Hamieh, Mohamad, primary, Mlecnik, Bernhard, primary, Kora, Hafid, primary, Bindea, Gabriela, primary, Angell, Helen K., primary, Fredriksen, Tessa, primary, Elie, Nicolas, primary, Fauquembergue, Emilie, primary, Drouet, Aurélie, primary, Leprince, Jérôme, primary, Benichou, Jacques, primary, Mauillon, Jacques, primary, Le Pessot, Florence, primary, Sesboüé, Richard, primary, Tuech, Jean-Jacques, primary, Sabourin, Jean-Christophe, primary, Michel, Pierre, primary, Frébourg, Thierry, primary, Galon, Jérôme, primary, and Latouche, Jean-Baptiste, primary

Published
2023
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7. Supplementary Figures 1-5, Tables 1-5 from Clinical Impact of Different Classes of Infiltrating T Cytotoxic and Helper Cells (Th1, Th2, Treg, Th17) in Patients with Colorectal Cancer

Author

Tosolini, Marie, primary, Kirilovsky, Amos, primary, Mlecnik, Bernhard, primary, Fredriksen, Tessa, primary, Mauger, Stéphanie, primary, Bindea, Gabriela, primary, Berger, Anne, primary, Bruneval, Patrick, primary, Fridman, Wolf-Herman, primary, Pagès, Franck, primary, and Galon, Jérôme, primary

Published
2023
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8. Data from Correlation between Density of CD8+ T-cell Infiltrate in Microsatellite Unstable Colorectal Cancers and Frameshift Mutations: A Rationale for Personalized Immunotherapy

Author

Maby, Pauline, primary, Tougeron, David, primary, Hamieh, Mohamad, primary, Mlecnik, Bernhard, primary, Kora, Hafid, primary, Bindea, Gabriela, primary, Angell, Helen K., primary, Fredriksen, Tessa, primary, Elie, Nicolas, primary, Fauquembergue, Emilie, primary, Drouet, Aurélie, primary, Leprince, Jérôme, primary, Benichou, Jacques, primary, Mauillon, Jacques, primary, Le Pessot, Florence, primary, Sesboüé, Richard, primary, Tuech, Jean-Jacques, primary, Sabourin, Jean-Christophe, primary, Michel, Pierre, primary, Frébourg, Thierry, primary, Galon, Jérôme, primary, and Latouche, Jean-Baptiste, primary

Published
2023
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9. Supplementary Figure 3 from Correlation between Density of CD8+ T-cell Infiltrate in Microsatellite Unstable Colorectal Cancers and Frameshift Mutations: A Rationale for Personalized Immunotherapy

Author

Maby, Pauline, primary, Tougeron, David, primary, Hamieh, Mohamad, primary, Mlecnik, Bernhard, primary, Kora, Hafid, primary, Bindea, Gabriela, primary, Angell, Helen K., primary, Fredriksen, Tessa, primary, Elie, Nicolas, primary, Fauquembergue, Emilie, primary, Drouet, Aurélie, primary, Leprince, Jérôme, primary, Benichou, Jacques, primary, Mauillon, Jacques, primary, Le Pessot, Florence, primary, Sesboüé, Richard, primary, Tuech, Jean-Jacques, primary, Sabourin, Jean-Christophe, primary, Michel, Pierre, primary, Frébourg, Thierry, primary, Galon, Jérôme, primary, and Latouche, Jean-Baptiste, primary

Published
2023
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10. Supplementary Figure Legend from Correlation between Density of CD8+ T-cell Infiltrate in Microsatellite Unstable Colorectal Cancers and Frameshift Mutations: A Rationale for Personalized Immunotherapy

Author

Maby, Pauline, primary, Tougeron, David, primary, Hamieh, Mohamad, primary, Mlecnik, Bernhard, primary, Kora, Hafid, primary, Bindea, Gabriela, primary, Angell, Helen K., primary, Fredriksen, Tessa, primary, Elie, Nicolas, primary, Fauquembergue, Emilie, primary, Drouet, Aurélie, primary, Leprince, Jérôme, primary, Benichou, Jacques, primary, Mauillon, Jacques, primary, Le Pessot, Florence, primary, Sesboüé, Richard, primary, Tuech, Jean-Jacques, primary, Sabourin, Jean-Christophe, primary, Michel, Pierre, primary, Frébourg, Thierry, primary, Galon, Jérôme, primary, and Latouche, Jean-Baptiste, primary

Published
2023
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11. Supplementary Table 1 from Correlation between Density of CD8+ T-cell Infiltrate in Microsatellite Unstable Colorectal Cancers and Frameshift Mutations: A Rationale for Personalized Immunotherapy

Author

Maby, Pauline, primary, Tougeron, David, primary, Hamieh, Mohamad, primary, Mlecnik, Bernhard, primary, Kora, Hafid, primary, Bindea, Gabriela, primary, Angell, Helen K., primary, Fredriksen, Tessa, primary, Elie, Nicolas, primary, Fauquembergue, Emilie, primary, Drouet, Aurélie, primary, Leprince, Jérôme, primary, Benichou, Jacques, primary, Mauillon, Jacques, primary, Le Pessot, Florence, primary, Sesboüé, Richard, primary, Tuech, Jean-Jacques, primary, Sabourin, Jean-Christophe, primary, Michel, Pierre, primary, Frébourg, Thierry, primary, Galon, Jérôme, primary, and Latouche, Jean-Baptiste, primary

Published
2023
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12. Supplementary Table 2 from Correlation between Density of CD8+ T-cell Infiltrate in Microsatellite Unstable Colorectal Cancers and Frameshift Mutations: A Rationale for Personalized Immunotherapy

Author

Maby, Pauline, primary, Tougeron, David, primary, Hamieh, Mohamad, primary, Mlecnik, Bernhard, primary, Kora, Hafid, primary, Bindea, Gabriela, primary, Angell, Helen K., primary, Fredriksen, Tessa, primary, Elie, Nicolas, primary, Fauquembergue, Emilie, primary, Drouet, Aurélie, primary, Leprince, Jérôme, primary, Benichou, Jacques, primary, Mauillon, Jacques, primary, Le Pessot, Florence, primary, Sesboüé, Richard, primary, Tuech, Jean-Jacques, primary, Sabourin, Jean-Christophe, primary, Michel, Pierre, primary, Frébourg, Thierry, primary, Galon, Jérôme, primary, and Latouche, Jean-Baptiste, primary

Published
2023
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13. Data from Clinical Impact of Different Classes of Infiltrating T Cytotoxic and Helper Cells (Th1, Th2, Treg, Th17) in Patients with Colorectal Cancer

Author

Tosolini, Marie, primary, Kirilovsky, Amos, primary, Mlecnik, Bernhard, primary, Fredriksen, Tessa, primary, Mauger, Stéphanie, primary, Bindea, Gabriela, primary, Berger, Anne, primary, Bruneval, Patrick, primary, Fridman, Wolf-Herman, primary, Pagès, Franck, primary, and Galon, Jérôme, primary

Published
2023
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14. Multicenter International Study of the Consensus Immunoscore for the Prediction of Relapse and Survival in Early-Stage Colon Cancer

Author

Mlecnik, Bernhard, primary, Lugli, Alessandro, additional, Bindea, Gabriela, additional, Marliot, Florence, additional, Bifulco, Carlo, additional, Lee, Jiun-Kae Jack, additional, Zlobec, Inti, additional, Rau, Tilman T., additional, Berger, Martin D., additional, Nagtegaal, Iris D., additional, Vink-Börger, Elisa, additional, Hartmann, Arndt, additional, Geppert, Carol I., additional, Kolwelter, Julie, additional, Merkel, Susanne, additional, Grützmann, Robert, additional, Van den Eynde, Marc, additional, Jouret-Mourin, Anne, additional, Kartheuser, Alex, additional, Léonard, Daniel, additional, Remue, Christophe, additional, Wang, Julia, additional, Bavi, Prashant, additional, Roehrl, Michael H. A., additional, Ohashi, Pamela S., additional, Nguyen, Linh T., additional, Han, SeongJun, additional, MacGregor, Heather L., additional, Hafezi-Bakhtiari, Sara, additional, Wouters, Bradly G., additional, Masucci, Giuseppe V., additional, Andersson, Emilia K., additional, Zavadova, Eva, additional, Vocka, Michal, additional, Spacek, Jan, additional, Petruzelka, Lubos, additional, Konopasek, Bohuslav, additional, Dundr, Pavel, additional, Skalova, Helena, additional, Nemejcova, Kristyna, additional, Botti, Gerardo, additional, Tatangelo, Fabiana, additional, Delrio, Paolo, additional, Ciliberto, Gennaro, additional, Maio, Michele, additional, Laghi, Luigi, additional, Grizzi, Fabio, additional, Fredriksen, Tessa, additional, Buttard, Bénédicte, additional, Lafontaine, Lucie, additional, Maby, Pauline, additional, Majdi, Amine, additional, Hijazi, Assia, additional, El Sissy, Carine, additional, Kirilovsky, Amos, additional, Berger, Anne, additional, Lagorce, Christine, additional, Paustian, Christopher, additional, Ballesteros-Merino, Carmen, additional, Dijkstra, Jeroen, additional, van de Water, Carlijn, additional, Vliet, Shannon van Lent-van, additional, Knijn, Nikki, additional, Mușină, Ana-Maria, additional, Scripcariu, Dragos-Viorel, additional, Popivanova, Boryana, additional, Xu, Mingli, additional, Fujita, Tomonobu, additional, Hazama, Shoichi, additional, Suzuki, Nobuaki, additional, Nagano, Hiroaki, additional, Okuno, Kiyotaka, additional, Torigoe, Toshihiko, additional, Sato, Noriyuki, additional, Furuhata, Tomohisa, additional, Takemasa, Ichiro, additional, Patel, Prabhu, additional, Vora, Hemangini H., additional, Shah, Birva, additional, Patel, Jayendrakumar B., additional, Rajvik, Kruti N., additional, Pandya, Shashank J., additional, Shukla, Shilin N., additional, Wang, Yili, additional, Zhang, Guanjun, additional, Kawakami, Yutaka, additional, Marincola, Francesco M., additional, Ascierto, Paolo A., additional, Fox, Bernard A., additional, Pagès, Franck, additional, and Galon, Jérôme, additional

Published
2023
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15. Clinical Performance of the Consensus Immunoscore in Colon Cancer in the Asian Population from the Multicenter International SITC Study

Author

Mlecnik, Bernhard, primary, Torigoe, Toshihiko, additional, Bindea, Gabriela, additional, Popivanova, Boryana, additional, Xu, Mingli, additional, Fujita, Tomonobu, additional, Hazama, Shoichi, additional, Suzuki, Nobuaki, additional, Nagano, Hiroaki, additional, Okuno, Kiyotaka, additional, Hirohashi, Yoshihiko, additional, Furuhata, Tomohisa, additional, Takemasa, Ichiro, additional, Patel, Prabhudas, additional, Vora, Hemangini, additional, Shah, Birva, additional, Patel, Jayendrakumar B., additional, Rajvik, Kruti N., additional, Pandya, Shashank J., additional, Shukla, Shilin N., additional, Wang, Yili, additional, Zhang, Guanjun, additional, Yoshino, Takayuki, additional, Taniguchi, Hiroya, additional, Bifulco, Carlo, additional, Lugli, Alessandro, additional, Lee, Jiun-Kae Jack, additional, Zlobec, Inti, additional, Rau, Tilman T., additional, Berger, Martin D., additional, Nagtegaal, Iris D., additional, Vink-Börger, Elisa, additional, Hartmann, Arndt, additional, Geppert, Carol I., additional, Kolwelter, Julie, additional, Merkel, Susanne, additional, Grützmann, Robert, additional, Van den Eynde, Marc, additional, Jouret-Mourin, Anne, additional, Kartheuser, Alex, additional, Léonard, Daniel, additional, Remue, Christophe, additional, Wang, Julia, additional, Bavi, Prashant, additional, Roehrl, Michael H. A., additional, Ohashi, Pamela S., additional, Nguyen, Linh T., additional, Han, SeongJun, additional, MacGregor, Heather L., additional, Hafezi-Bakhtiari, Sara, additional, Wouters, Bradly G., additional, Masucci, Giuseppe V., additional, Andersson, Emilia, additional, Zavadova, Eva, additional, Vocka, Michal, additional, Spacek, Jan, additional, Petruzelka, Lubos, additional, Konopasek, Bohuslav, additional, Dundr, Pavel, additional, Skalova, Helena, additional, Nemejcova, Kristyna, additional, Botti, Gerardo, additional, Tatangelo, Fabiana, additional, Delrio, Paolo, additional, Ciliberto, Gennaro, additional, Maio, Michele, additional, Laghi, Luigi, additional, Grizzi, Fabio, additional, Marliot, Florence, additional, Fredriksen, Tessa, additional, Buttard, Bénédicte, additional, Lafontaine, Lucie, additional, Maby, Pauline, additional, Majdi, Amine, additional, Hijazi, Assia, additional, El Sissy, Carine, additional, Kirilovsky, Amos, additional, Berger, Anne, additional, Lagorce, Christine, additional, Paustian, Christopher, additional, Ballesteros-Merino, Carmen, additional, Dijkstra, Jeroen, additional, Van de Water, Carlijn, additional, van Lent-van Vliet, Shannon, additional, Knijn, Nikki, additional, Mușină, Ana-Maria, additional, Scripcariu, Dragos-Viorel, additional, Marincola, Francesco M., additional, Ascierto, Paolo A., additional, Fox, Bernard A., additional, Pagès, Franck, additional, Kawakami, Yutaka, additional, and Galon, Jérôme, additional

Published
2022
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16. Clinical Performance of the Consensus Immunoscore in Colon Cancer in the Asian Population from the Multicenter International SITC Study.

Author

UCL - SSS/IREC/MIRO - Pôle d'imagerie moléculaire, radiothérapie et oncologie, UCL - (SLuc) Unité d'oncologie médicale, UCL - (SLuc) Service d'anatomie pathologique, UCL - SSS/IREC/CHEX - Pôle de chirgurgie expérimentale et transplantation, UCL - (SLuc) Service de chirurgie et transplantation abdominale, Mlecnik, Bernhard, Torigoe, Toshihiko, Bindea, Gabriela, Popivanova, Boryana, Xu, Mingli, Fujita, Tomonobu, Hazama, Shoichi, Suzuki, Nobuaki, Nagano, Hiroaki, Okuno, Kiyotaka, Hirohashi, Yoshihiko, Furuhata, Tomohisa, Takemasa, Ichiro, Patel, Prabhudas, Vora, Hemangini, Shah, Birva, Patel, Jayendrakumar B, Rajvik, Kruti N, Pandya, Shashank J, Shukla, Shilin N, Wang, Yili, Zhang, Guanjun, Yoshino, Takayuki, Taniguchi, Hiroya, Bifulco, Carlo, Lugli, Alessandro, Lee, Jiun-Kae Jack, Zlobec, Inti, Rau, Tilman T, Berger, Martin D, Nagtegaal, Iris D, Vink-Börger, Elisa, Hartmann, Arndt, Geppert, Carol I, Kolwelter, Julie, Merkel, Susanne, Grützmann, Robert, Van den Eynde, Marc, Jouret-Mourin, Anne, Kartheuser, Alex, Léonard, Daniel, Remue, Christophe, Wang, Julia, Bavi, Prashant, Roehrl, Michael H A, Ohashi, Pamela S, Nguyen, Linh T, Han, SeongJun, MacGregor, Heather L, Hafezi-Bakhtiari, Sara, Wouters, Bradly G, Masucci, Giuseppe V, Andersson, Emilia, Zavadova, Eva, Vocka, Michal, Spacek, Jan, Petruzelka, Lubos, Konopasek, Bohuslav, Dundr, Pavel, Skalova, Helena, Nemejcova, Kristyna, Botti, Gerardo, Tatangelo, Fabiana, Delrio, Paolo, Ciliberto, Gennaro, Maio, Michele, Laghi, Luigi, Grizzi, Fabio, Marliot, Florence, Fredriksen, Tessa, Buttard, Bénédicte, Lafontaine, Lucie, Maby, Pauline, Majdi, Amine, Hijazi, Assia, El Sissy, Carine, Kirilovsky, Amos, Berger, Anne, Lagorce, Christine, Paustian, Christopher, Ballesteros-Merino, Carmen, Dijkstra, Jeroen, Van de Water, Carlijn, van Lent-van Vliet, Shannon, Knijn, Nikki, Mușină, Ana-Maria, Scripcariu, Dragos-Viorel, Marincola, Francesco M, Ascierto, Paolo A, Fox, Bernard A, Pagès, Franck, Kawakami, Yutaka, Galon, Jérôme, UCL - SSS/IREC/MIRO - Pôle d'imagerie moléculaire, radiothérapie et oncologie, UCL - (SLuc) Unité d'oncologie médicale, UCL - (SLuc) Service d'anatomie pathologique, UCL - SSS/IREC/CHEX - Pôle de chirgurgie expérimentale et transplantation, UCL - (SLuc) Service de chirurgie et transplantation abdominale, Mlecnik, Bernhard, Torigoe, Toshihiko, Bindea, Gabriela, Popivanova, Boryana, Xu, Mingli, Fujita, Tomonobu, Hazama, Shoichi, Suzuki, Nobuaki, Nagano, Hiroaki, Okuno, Kiyotaka, Hirohashi, Yoshihiko, Furuhata, Tomohisa, Takemasa, Ichiro, Patel, Prabhudas, Vora, Hemangini, Shah, Birva, Patel, Jayendrakumar B, Rajvik, Kruti N, Pandya, Shashank J, Shukla, Shilin N, Wang, Yili, Zhang, Guanjun, Yoshino, Takayuki, Taniguchi, Hiroya, Bifulco, Carlo, Lugli, Alessandro, Lee, Jiun-Kae Jack, Zlobec, Inti, Rau, Tilman T, Berger, Martin D, Nagtegaal, Iris D, Vink-Börger, Elisa, Hartmann, Arndt, Geppert, Carol I, Kolwelter, Julie, Merkel, Susanne, Grützmann, Robert, Van den Eynde, Marc, Jouret-Mourin, Anne, Kartheuser, Alex, Léonard, Daniel, Remue, Christophe, Wang, Julia, Bavi, Prashant, Roehrl, Michael H A, Ohashi, Pamela S, Nguyen, Linh T, Han, SeongJun, MacGregor, Heather L, Hafezi-Bakhtiari, Sara, Wouters, Bradly G, Masucci, Giuseppe V, Andersson, Emilia, Zavadova, Eva, Vocka, Michal, Spacek, Jan, Petruzelka, Lubos, Konopasek, Bohuslav, Dundr, Pavel, Skalova, Helena, Nemejcova, Kristyna, Botti, Gerardo, Tatangelo, Fabiana, Delrio, Paolo, Ciliberto, Gennaro, Maio, Michele, Laghi, Luigi, Grizzi, Fabio, Marliot, Florence, Fredriksen, Tessa, Buttard, Bénédicte, Lafontaine, Lucie, Maby, Pauline, Majdi, Amine, Hijazi, Assia, El Sissy, Carine, Kirilovsky, Amos, Berger, Anne, Lagorce, Christine, Paustian, Christopher, Ballesteros-Merino, Carmen, Dijkstra, Jeroen, Van de Water, Carlijn, van Lent-van Vliet, Shannon, Knijn, Nikki, Mușină, Ana-Maria, Scripcariu, Dragos-Viorel, Marincola, Francesco M, Ascierto, Paolo A, Fox, Bernard A, Pagès, Franck, Kawakami, Yutaka, and Galon, Jérôme

Abstract

In this study, we evaluated the prognostic value of Immunoscore in patients with stage I-III colon cancer (CC) in the Asian population. These patients were originally included in an international study led by the Society for Immunotherapy of Cancer (SITC) on 2681 patients with AJCC/UICC-TNM stages I-III CC. CD3+ and cytotoxic CD8+ T-lymphocyte densities were quantified in the tumor and invasive margin by digital pathology. The association of Immunoscore with prognosis was evaluated for time to recurrence (TTR), disease-free survival (DFS), and overall survival (OS). Immunoscore stratified Asian patients (n = 423) into different risk categories and was not impacted by age. Recurrence-free rates at 3 years were 78.5%, 85.2%, and 98.3% for a Low, Intermediate, and High Immunoscore, respectively (HR[Low-vs-High] = 7.26 (95% CI 1.75-30.19); = 0.0064). A High Immunoscore showed a significant association with prolonged TTR, OS, and DFS ( < 0.05). In Cox multivariable analysis stratified by center, Immunoscore association with TTR was independent (HR[Low-vs-Int+High] = 2.22 (95% CI 1.10-4.55) = 0.0269) of the patient's gender, T-stage, N-stage, sidedness, and MSI status. A significant association of a High Immunoscore with prolonged TTR was also found among MSS (HR[Low-vs-Int+High] = 4.58 (95% CI 2.27-9.23); ≤ 0.0001), stage II (HR[Low-vs-Int+High] = 2.72 (95% CI 1.35-5.51); = 0.0052), low-risk stage-II (HR[Low-vs-Int+High] = 2.62 (95% CI 1.21-5.68); = 0.0146), and high-risk stage II patients (HR[Low-vs-Int+High] = 3.11 (95% CI 1.39-6.91); = 0.0055). A High Immunoscore is significantly associated with the prolonged survival of CC patients within the Asian population.

Published
2022

17. An Autologous Dendritic Cell Vaccine Promotes Anticancer Immunity in Patients with Ovarian Cancer with Low Mutational Burden and Cold Tumors

Author

Fucikova, Jitka, primary, Hensler, Michal, additional, Kasikova, Lenka, additional, Lanickova, Tereza, additional, Pasulka, Josef, additional, Rakova, Jana, additional, Drozenova, Jana, additional, Fredriksen, Tessa, additional, Hraska, Marek, additional, Hrnciarova, Tereza, additional, Sochorova, Klara, additional, Rozkova, Daniela, additional, Sojka, Ludek, additional, Dundr, Pavel, additional, Laco, Jan, additional, Brtnicky, Tomas, additional, Praznovec, Ivan, additional, Halaska, Michael J., additional, Rob, Lukas, additional, Ryska, Ales, additional, Coosemans, An, additional, Vergote, Ignace, additional, Cibula, David, additional, Bartunkova, Jirina, additional, Galon, Jérôme, additional, Galluzzi, Lorenzo, additional, and Spisek, Radek, additional

Published
2022
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18. Integrative Analyses of Colorectal Cancer Show Immunoscore Is a Stronger Predictor of Patient Survival Than Microsatellite Instability

Author

Mlecnik, Bernhard, Bindea, Gabriela, Angell, Helen K., Maby, Pauline, Angelova, Mihaela, Tougeron, David, Church, Sarah E., Lafontaine, Lucie, Fischer, Maria, Fredriksen, Tessa, Sasso, Maristella, Bilocq, Amélie M., Kirilovsky, Amos, Obenauf, Anna C., Hamieh, Mohamad, Berger, Anne, Bruneval, Patrick, Tuech, Jean-Jacques, Sabourin, Jean-Christophe, Le Pessot, Florence, Mauillon, Jacques, Rafii, Arash, Laurent-Puig, Pierre, Speicher, Michael R., Trajanoski, Zlatko, Michel, Pierre, Sesboüe, Richard, Frebourg, Thierry, Pagès, Franck, Valge-Archer, Viia, Latouche, Jean-Baptiste, and Galon, Jérôme

Published
2016
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20. Multicenter International Society for Immunotherapy of Cancer Study of the Consensus Immunoscore for the Prediction of Survival and Response to Chemotherapy in Stage III Colon Cancer

Author

Mlecnik, Bernhard, primary, Bifulco, Carlo, additional, Bindea, Gabriela, additional, Marliot, Florence, additional, Lugli, Alessandro, additional, Lee, J. Jack, additional, Zlobec, Inti, additional, Rau, Tilman T., additional, Berger, Martin D., additional, Nagtegaal, Iris D., additional, Vink-Börger, Elisa, additional, Hartmann, Arndt, additional, Geppert, Carol, additional, Kolwelter, Julie, additional, Merkel, Susanne, additional, Grützmann, Robert, additional, Van den Eynde, Marc, additional, Jouret-Mourin, Anne, additional, Kartheuser, Alex, additional, Léonard, Daniel, additional, Remue, Christophe, additional, Wang, Julia Y., additional, Bavi, Prashant, additional, Roehrl, Michael H. A., additional, Ohashi, Pamela S., additional, Nguyen, Linh T., additional, Han, SeongJun, additional, MacGregor, Heather L., additional, Hafezi-Bakhtiari, Sara, additional, Wouters, Bradly G., additional, Masucci, Giuseppe V., additional, Andersson, Emilia K., additional, Zavadova, Eva, additional, Vocka, Michal, additional, Spacek, Jan, additional, Petruzelka, Lubos, additional, Konopasek, Bohuslav, additional, Dundr, Pavel, additional, Skalova, Helena, additional, Nemejcova, Kristyna, additional, Botti, Gerardo, additional, Tatangelo, Fabiana, additional, Delrio, Paolo, additional, Ciliberto, Gennaro, additional, Maio, Michele, additional, Laghi, Luigi, additional, Grizzi, Fabio, additional, Fredriksen, Tessa, additional, Buttard, Bénédicte, additional, Lafontaine, Lucie, additional, Bruni, Daniela, additional, Lanzi, Anastasia, additional, El Sissy, Carine, additional, Haicheur, Nacilla, additional, Kirilovsky, Amos, additional, Berger, Anne, additional, Lagorce, Christine, additional, Paustian, Christopher, additional, Ballesteros-Merino, Carmen, additional, Dijkstra, Jeroen, additional, van de Water, Carlijn, additional, van Lent–van Vliet, Shannon, additional, Knijn, Nikki, additional, Muşină, Ana-Maria, additional, Scripcariu, Dragos-Viorel, additional, Popivanova, Boryana, additional, Xu, Mingli, additional, Fujita, Tomonobu, additional, Hazama, Shoichi, additional, Suzuki, Nobuaki, additional, Nagano, Hiroaki, additional, Okuno, Kiyotaka, additional, Torigoe, Toshihiko, additional, Sato, Noriyuki, additional, Furuhata, Tomohisa, additional, Takemasa, Ichiro, additional, Itoh, Kyogo, additional, Patel, Prabhu S., additional, Vora, Hemangini H., additional, Shah, Birva, additional, Patel, Jayendrakumar B., additional, Rajvik, Kruti N., additional, Pandya, Shashank J., additional, Shukla, Shilin N., additional, Wang, Yili, additional, Zhang, Guanjun, additional, Kawakami, Yutaka, additional, Marincola, Francesco M., additional, Ascierto, Paolo A., additional, Fox, Bernard A., additional, Pagès, Franck, additional, and Galon, Jérôme, additional

Published
2020
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21. A Diagnostic Biopsy-Adapted Immunoscore Predicts Response to Neoadjuvant Treatment and Selects Patients with Rectal Cancer Eligible for a Watch-and-Wait Strategy

Author

El Sissy, Carine, primary, Kirilovsky, Amos, additional, Van den Eynde, Marc, additional, Muşină, Ana-Maria, additional, Anitei, Maria-Gabriela, additional, Romero, Alfredo, additional, Marliot, Florence, additional, Junca, Audelaure, additional, Doyen, Jérôme, additional, Mlecnik, Bernhard, additional, Haicheur, Nacilla, additional, Fredriksen, Tessa, additional, Lagorce, Christine, additional, Jouret-Mourin, Anne, additional, Leonard, Daniel, additional, Bibeau, Frédéric, additional, Iseas, Soledad, additional, Roca, Enrique L., additional, Cabanne, Ana M., additional, Vaccaro, Carlos A., additional, Santino, Juan P., additional, Huertas, Eduardo, additional, Tougeron, David, additional, Carvalho, Carlos, additional, Figueiredo, Nuno, additional, Perez, Rodrigo O., additional, Habr-Gama, Angelita, additional, Scripcariu, Viorel, additional, Gerard, Jean-Pierre, additional, Galon, Jérôme, additional, Zeitoun, Guy, additional, and Pagès, Franck, additional

Published
2020
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22. Prognostic assessment of resected colorectal liver metastases integrating pathological features,RASmutation and Immunoscore

Author

Baldin, Pamela, primary, Van den Eynde, Marc, additional, Mlecnik, Bernhard, additional, Bindea, Gabriela, additional, Beniuga, Gabriela, additional, Carrasco, Javier, additional, Haicheur, Nacilla, additional, Marliot, Florence, additional, Lafontaine, Lucie, additional, Fredriksen, Tessa, additional, Lanthier, Nicolas, additional, Hubert, Catherine, additional, Navez, Benoît, additional, Huyghe, Nicolas, additional, Pagès, Franck, additional, Jouret‐Mourin, Anne, additional, Galon, Jérôme, additional, and Komuta, Mina, additional

Published
2020
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23. TCF4 Deletions in Pitt-Hopkins Syndrome

Author

Giurgea, Irina, Missirian, Chantal, Cacciagli, Pierre, Whalen, Sandra, Fredriksen, Tessa, Gaillon, Thierry, Rankin, Julia, Mathieu-Dramard, Michele, Morin, Gilles, Martin-Coignard, Dominique, Dubourg, Christèle, Chabrol, Brigitte, Arfi, Jacqueline, Giuliano, Fabienne, Lambert, Jean Claude, Philip, Nicole, Sarda, Pierre, Villard, Laurent, Goossens, Michel, and Moncla, Anne

Published
2008
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24. Abstract 4574: Combining multimodal biomarkers as an immunogram to guide immunotherapy use: A proof of concept

Author

Sbarrato, Thomas, primary, Sudre, Lucie, additional, Vanhille, Laurent, additional, Outters, Pernelle, additional, Angelova, Mihaela, additional, Mlecnik, Bernhard, additional, Vasaturo, Angela, additional, Bindea, Gabriela, additional, Fredriksen, Tessa, additional, Lafontaine, Lucie, additional, Bruni, Daniela, additional, Galon, Jérôme, additional, and Fieschi, Jacques, additional

Published
2019
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25. Comprehensive Intrametastatic Immune Quantification and Major Impact of Immunoscore on Survival.

Author

UCL - (SLuc) Service d'anatomie pathologique, Mlecnik, Bernhard, Van den Eynde, Marc, Bindea, Gabriela, Church, Sarah E, Vasaturo, Angela, Fredriksen, Tessa, Lafontaine, Lucie, Haicheur, Nacilla, Marliot, Florence, Debetancourt, Daphné, Pairet, Géraldine, Mourin, Anne, Gigot, Jean-Francois, Hubert, Catherine, Danse, Etienne, Dragean, Cristina, Carrasco, Javier, Humblet, Yves, Valge-Archer, Viia, Berger, Anne, Pagès, Franck, Machiels, Jean-Pascal, Galon, Jérôme, UCL - (SLuc) Service d'anatomie pathologique, Mlecnik, Bernhard, Van den Eynde, Marc, Bindea, Gabriela, Church, Sarah E, Vasaturo, Angela, Fredriksen, Tessa, Lafontaine, Lucie, Haicheur, Nacilla, Marliot, Florence, Debetancourt, Daphné, Pairet, Géraldine, Mourin, Anne, Gigot, Jean-Francois, Hubert, Catherine, Danse, Etienne, Dragean, Cristina, Carrasco, Javier, Humblet, Yves, Valge-Archer, Viia, Berger, Anne, Pagès, Franck, Machiels, Jean-Pascal, and Galon, Jérôme

Abstract

This study assesses how the metastatic immune landscape is impacting the response to treatment and the outcome of colorectal cancer (CRC) patients. Complete curative resection of metastases (n = 441) was performed for two patient cohorts (n = 153). Immune densities were quantified in the center and invasive margin of all metastases. Immunoscore and T and B cell (TB) score were analyzed in relation to radiological and pathological responses and patient's disease-free (DFS) and overall survival (OS) using multivariable Cox proportional hazards models. All statistical tests were two-sided. The spatial distribution of immune cells within metastases was nonuniform. Patients, as well as metastases of the same patient, had variable immune infiltrates and response to therapy. A beneficial response was statistically significantly associated with increased immune densities. Among all metastases, Immunoscore (I) and TB score evaluated in the least immune-infiltrated metastases were the strongest predictors for DFS and OS (five-year follow-up, Immunoscore: I 3-4: DFS rate = 27.9%, 95% CI = 15.2 to 51.3; vs I 0-1-2: DFS rate = 12.3%, 95% CI = 4.9 to 30.6; HR = 0.45, 95% CI = 0.28 to 0.70, P = .02; I 3-4: OS rate = 64.6%, 95% CI = 46.6 to 89.6; vs I 0-1-2: OS rate = 32.5%, 95% CI = 17.2 to 61.4; HR = 0.32, 95% CI = 0.15 to 0.66, P = .001, C-index = 65.9%; five-year follow-up, TB score: TB 3-4: DFS rate = 25.7%, 95% CI = 14.2 to 46.6; vs TB 0-1-2: DFS rate = 5.0%, 95% CI = 0.8 to 32.4; HR = 0.36, 95% CI = 0.22 to 0.57, P < .001; TB 3-4: OS rate = 63.7%, 95% CI = 46.4 to 87.5; vs TB 0-1-2: OS rate: 21.4%, 95% CI = 9.2 to 49.8; HR = 0.25, 95% CI = 0.12 to 0.51, P < .001, C-index = 67.8%). High TB score and Immunoscore patients had a median survival of 70.5 months, while low patients survived only 25.1 to 38.3 months. Nonresponding patients with high-immune infiltrates had prolonged DFS (HR = 0.28, 95% CI = 0.15 to 0.52, P = .001) and OS (HR = 0.25, 95% CI = 0.1 to 0.62, P = .001). T

Published
2018

26. Evolution of Metastases in Space and Time under Immune Selection.

Author

UCL - SSS/IREC/CHEX - Pôle de chirgurgie expérimentale et transplantation, UCL - SSS/IREC/MIRO - Pôle d'imagerie moléculaire, radiothérapie et oncologie, UCL - (SLuc) Service d'anatomie pathologique, UCL - (SLuc) Service de chirurgie et transplantation abdominale, UCL - (SLuc) Unité d'oncologie médicale, Angelova, Mihaela, Mlecnik, Bernhard, Vasaturo, Angela, Bindea, Gabriela, Fredriksen, Tessa, Lafontaine, Lucie, Buttard, Bénédicte, Morgand, Erwan, Bruni, Daniela, Mourin, Anne, Hubert, Catherine, Kartheuser, Alex, Humblet, Yves, Ceccarelli, Michele, Syed, Najeeb, Marincola, Francesco M, Bedognetti, Davide, Van den Eynde, Marc, Galon, Jérôme, UCL - SSS/IREC/CHEX - Pôle de chirgurgie expérimentale et transplantation, UCL - SSS/IREC/MIRO - Pôle d'imagerie moléculaire, radiothérapie et oncologie, UCL - (SLuc) Service d'anatomie pathologique, UCL - (SLuc) Service de chirurgie et transplantation abdominale, UCL - (SLuc) Unité d'oncologie médicale, Angelova, Mihaela, Mlecnik, Bernhard, Vasaturo, Angela, Bindea, Gabriela, Fredriksen, Tessa, Lafontaine, Lucie, Buttard, Bénédicte, Morgand, Erwan, Bruni, Daniela, Mourin, Anne, Hubert, Catherine, Kartheuser, Alex, Humblet, Yves, Ceccarelli, Michele, Syed, Najeeb, Marincola, Francesco M, Bedognetti, Davide, Van den Eynde, Marc, and Galon, Jérôme

Abstract

We examined how the immune microenvironment molds tumor evolution at different metastatic organs in a longitudinal dataset of colorectal cancer. Through multiplexed analyses, we showed that clonal evolution patterns during metastatic progression depend on the immune contexture at the metastatic site. Genetic evidence of neoantigen depletion was observed in the sites with high Immunoscore and spatial proximity between Ki67 tumor cells and CD3 cells. The immunoedited tumor clones were eliminated and did not recur, while progressing clones were immune privileged, despite the presence of tumor-infiltrating lymphocytes. Characterization of immune-privileged metastases revealed tumor-intrinsic and tumor-extrinsic mechanisms of escape. The lowest recurrence risk was associated with high Immunoscore, occurrence of immunoediting, and low tumor burden. We propose a parallel selection model of metastatic progression, where branched evolution could be traced back to immune-escaping clones. The findings could inform the understanding of cancer dissemination and the development of immunotherapeutics.

Published
2018

27. The Link between the Multiverse of Immune Microenvironments in Metastases and the Survival of Colorectal Cancer Patients.

Author

UCL - SSS/IREC/MIRO - Pôle d'imagerie moléculaire, radiothérapie et oncologie, UCL - SSS/IREC/GAEN - Pôle d'Hépato-gastro-entérologie, UCL - SSS/IREC/CHEX - Pôle de chirgurgie expérimentale et transplantation, UCL - (SLuc) Service de chirurgie et transplantation abdominale, UCL - (SLuc) Service d'anatomie pathologique, UCL - (SLuc) Unité d'oncologie médicale, UCL - (SLuc) Centre du cancer, Van den Eynde, Marc, Mlecnik, Bernhard, Bindea, Gabriela, Fredriksen, Tessa, Church, Sarah E, Lafontaine, Lucie, Haicheur, Nacilla, Marliot, Florence, Angelova, Mihaela, Vasaturo, Angela, Bruni, Daniela, Mourin, Anne, Baldin, Paméla, Huyghe, Nicolas, Haustermans, Karin, Debucquoy, Annelies, Van Cutsem, Eric, Gigot, Jean-François, Hubert, Catherine, Kartheuser, Alex, Remue, Christophe, Léonard, Daniel, Valge-Archer, Viia, Pagès, Franck, Machiels, Jean-Pascal, Galon, Jérôme, UCL - SSS/IREC/MIRO - Pôle d'imagerie moléculaire, radiothérapie et oncologie, UCL - SSS/IREC/GAEN - Pôle d'Hépato-gastro-entérologie, UCL - SSS/IREC/CHEX - Pôle de chirgurgie expérimentale et transplantation, UCL - (SLuc) Service de chirurgie et transplantation abdominale, UCL - (SLuc) Service d'anatomie pathologique, UCL - (SLuc) Unité d'oncologie médicale, UCL - (SLuc) Centre du cancer, Van den Eynde, Marc, Mlecnik, Bernhard, Bindea, Gabriela, Fredriksen, Tessa, Church, Sarah E, Lafontaine, Lucie, Haicheur, Nacilla, Marliot, Florence, Angelova, Mihaela, Vasaturo, Angela, Bruni, Daniela, Mourin, Anne, Baldin, Paméla, Huyghe, Nicolas, Haustermans, Karin, Debucquoy, Annelies, Van Cutsem, Eric, Gigot, Jean-François, Hubert, Catherine, Kartheuser, Alex, Remue, Christophe, Léonard, Daniel, Valge-Archer, Viia, Pagès, Franck, Machiels, Jean-Pascal, and Galon, Jérôme

Abstract

Treatment of metastatic colorectal cancer is based upon the assumption that metastases are homogeneous within a patient. We quantified immune cell types of 603 whole-slide metastases and primary colorectal tumors from 222 patients. Primary lesions, and synchronous and metachronous metastases, had a heterogeneous immune infiltrate and mutational diversity. Small metastases had frequently a low Immunoscore and T and B cell score, while a high Immunoscore was associated with a lower number of metastases. Anti-epidermal growth factor receptor treatment modified immune gene expression and significantly increased T cell densities in the metastasis core. The predictive accuracy of the Immunoscore from a single biopsy was superior to the one of programmed cell death ligand 1 (PD-L1). The immune phenotype of the least-infiltrated metastasis had a stronger association with patient outcome than other metastases.

Published
2018

28. Prognostic assessment of resected colorectal liver metastases integrating pathological features, RAS mutation and Immunoscore.

Author

Baldin, Pamela, Van den Eynde, Marc, Mlecnik, Bernhard, Bindea, Gabriela, Beniuga, Gabriela, Carrasco, Javier, Haicheur, Nacilla, Marliot, Florence, Lafontaine, Lucie, Fredriksen, Tessa, Lanthier, Nicolas, Hubert, Catherine, Navez, Benoît, Huyghe, Nicolas, Pagès, Franck, Jouret‐Mourin, Anne, Galon, Jérôme, and Komuta, Mina

Subjects
LIVER metastasis, PROGNOSIS, COLON cancer, PROGRESSION-free survival, PROPORTIONAL hazards models, SURGICAL excision, LIVER
Abstract

Surgical resection of colorectal liver metastases combined with systemic treatment aims to maximize patient survival. However, recurrence rates are very high postsurgery. In order to assess patient prognosis after metastasis resection, we evaluated the main patho‐molecular and immune parameters of all surgical specimens. Two hundred twenty‐one patients who underwent, after different preoperative treatment, curative resection of 582 metastases were analyzed. Clinicopathological parameters, RAS tumor mutation, and the consensus Immunoscore (I) were assessed for all patients. Overall survival (OS) and time to relapse (TTR) were estimated using the Kaplan–Meier method and compared by log‐rank tests. Cox proportional hazard models were used for uni‐ and multivariate analysis. Immunoscore and clinicopathological parameters (number of metastases, surgical margin, histopathological growth pattern, and steatohepatitis) were associated with relapse in multivariate analysis. Overall, pathological score (PS) that combines relevant clinicopathological factors for relapse, and I, were prognostic for TTR (2‐year TTR rate PS 0–1: 49.8.% (95% CI: 42.2–58.8) versus PS 2–4: 20.9% (95% CI: 13.4–32.8), hazard ratio (HR) = 2.54 (95% CI: 1.82–3.53), p < 0.0000; and 2‐year TTR rate I 0: 25.7% (95% CI: 16.3–40.5) versus I 3–4: 60% (95% CI: 47.2–76.3), HR = 2.87 (95% CI: 1.73–4.75), p = 0.0000). Immunoscore was also prognostic for OS (HR [I 3–4 versus I 0] = 4.25, 95% CI: 1.95–9.23; p = 0.0001). Immunoscore (HR [I 3–4 versus I 0] = 0.27, 95% CI: 0.12–0.58; p = 0.0009) and RAS mutation (HR [mutated versus WT] = 1.66, 95% CI: 1.06–2.58; p = 0.0265) were significant for OS. In conclusion, PS including relevant clinicopathological parameters and Immunoscore permit stratification of stage IV colorectal cancer patient prognosis in terms of TTR and identify patients with higher risk of recurrence. Immunoscore remains the major prognostic factor for OS. [ABSTRACT FROM AUTHOR]

Published
2021
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29. The Link between the Multiverse of Immune Microenvironments in Metastases and the Survival of Colorectal Cancer Patients

Author

Van den Eynde, Marc, primary, Mlecnik, Bernhard, additional, Bindea, Gabriela, additional, Fredriksen, Tessa, additional, Church, Sarah E., additional, Lafontaine, Lucie, additional, Haicheur, Nacilla, additional, Marliot, Florence, additional, Angelova, Mihaela, additional, Vasaturo, Angela, additional, Bruni, Daniela, additional, Jouret-Mourin, Anne, additional, Baldin, Pamela, additional, Huyghe, Nicolas, additional, Haustermans, Karin, additional, Debucquoy, Annelies, additional, Van Cutsem, Eric, additional, Gigot, Jean-Francois, additional, Hubert, Catherine, additional, Kartheuser, Alex, additional, Remue, Christophe, additional, Léonard, Daniel, additional, Valge-Archer, Viia, additional, Pagès, Franck, additional, Machiels, Jean-Pascal, additional, and Galon, Jérôme, additional

Published
2018
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30. Evolution of Metastases in Space and Time under Immune Selection

Author

Angelova, Mihaela, primary, Mlecnik, Bernhard, additional, Vasaturo, Angela, additional, Bindea, Gabriela, additional, Fredriksen, Tessa, additional, Lafontaine, Lucie, additional, Buttard, Bénédicte, additional, Morgand, Erwan, additional, Bruni, Daniela, additional, Jouret-Mourin, Anne, additional, Hubert, Catherine, additional, Kartheuser, Alex, additional, Humblet, Yves, additional, Ceccarelli, Michele, additional, Syed, Najeeb, additional, Marincola, Francesco M., additional, Bedognetti, Davide, additional, Van den Eynde, Marc, additional, and Galon, Jérôme, additional

Published
2018
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31. International validation of the consensus Immunoscore for the classification of colon cancer: a prognostic and accuracy study

Author

Pagès, Franck, primary, Mlecnik, Bernhard, additional, Marliot, Florence, additional, Bindea, Gabriela, additional, Ou, Fang-Shu, additional, Bifulco, Carlo, additional, Lugli, Alessandro, additional, Zlobec, Inti, additional, Rau, Tilman T, additional, Berger, Martin D, additional, Nagtegaal, Iris D, additional, Vink-Börger, Elisa, additional, Hartmann, Arndt, additional, Geppert, Carol, additional, Kolwelter, Julie, additional, Merkel, Susanne, additional, Grützmann, Robert, additional, Van den Eynde, Marc, additional, Jouret-Mourin, Anne, additional, Kartheuser, Alex, additional, Léonard, Daniel, additional, Remue, Christophe, additional, Wang, Julia Y, additional, Bavi, Prashant, additional, Roehrl, Michael H A, additional, Ohashi, Pamela S, additional, Nguyen, Linh T, additional, Han, SeongJun, additional, MacGregor, Heather L, additional, Hafezi-Bakhtiari, Sara, additional, Wouters, Bradly G, additional, Masucci, Giuseppe V, additional, Andersson, Emilia K, additional, Zavadova, Eva, additional, Vocka, Michal, additional, Spacek, Jan, additional, Petruzelka, Lubos, additional, Konopasek, Bohuslav, additional, Dundr, Pavel, additional, Skalova, Helena, additional, Nemejcova, Kristyna, additional, Botti, Gerardo, additional, Tatangelo, Fabiana, additional, Delrio, Paolo, additional, Ciliberto, Gennaro, additional, Maio, Michele, additional, Laghi, Luigi, additional, Grizzi, Fabio, additional, Fredriksen, Tessa, additional, Buttard, Bénédicte, additional, Angelova, Mihaela, additional, Vasaturo, Angela, additional, Maby, Pauline, additional, Church, Sarah E, additional, Angell, Helen K, additional, Lafontaine, Lucie, additional, Bruni, Daniela, additional, El Sissy, Carine, additional, Haicheur, Nacilla, additional, Kirilovsky, Amos, additional, Berger, Anne, additional, Lagorce, Christine, additional, Meyers, Jeffrey P, additional, Paustian, Christopher, additional, Feng, Zipei, additional, Ballesteros-Merino, Carmen, additional, Dijkstra, Jeroen, additional, van de Water, Carlijn, additional, van Lent-van Vliet, Shannon, additional, Knijn, Nikki, additional, Mușină, Ana-Maria, additional, Scripcariu, Dragos-Viorel, additional, Popivanova, Boryana, additional, Xu, Mingli, additional, Fujita, Tomonobu, additional, Hazama, Shoichi, additional, Suzuki, Nobuaki, additional, Nagano, Hiroaki, additional, Okuno, Kiyotaka, additional, Torigoe, Toshihiko, additional, Sato, Noriyuki, additional, Furuhata, Tomohisa, additional, Takemasa, Ichiro, additional, Itoh, Kyogo, additional, Patel, Prabhu S, additional, Vora, Hemangini H, additional, Shah, Birva, additional, Patel, Jayendrakumar B, additional, Rajvik, Kruti N, additional, Pandya, Shashank J, additional, Shukla, Shilin N, additional, Wang, Yili, additional, Zhang, Guanjun, additional, Kawakami, Yutaka, additional, Marincola, Francesco M, additional, Ascierto, Paolo A, additional, Sargent, Daniel J, additional, Fox, Bernard A, additional, and Galon, Jérôme, additional

Published
2018
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32. Metastatic colorectal cancer has heterogeneous immune microenvironment and mutational expression

Author

Van den Eynde, Marc, Mlecnik, Bernhard, Bindea, Gabriela, Fredriksen, Tessa, Lafontaine, Lucie, Haicheur, Nacilla, Marliot, Florence, Debetancourt, Daphné, Mourin, Anne, Sempoux, Christine, Gigot, Jean-François, Hubert, Catherine, Kartheuser, Alex, Remue, Christophe, Léonard, Daniel, Carrasco, Javier, Humblet, Yves, Pages, Franck, Machiels, Jean-Pascal, Galon, Jerome, Belgian Week of Gastroenterology - XXVIIIth edition, UCL - SSS/IREC/GAEN - Pôle d'Hépato-gastro-entérologie, UCL - SSS/IREC/MIRO - Pôle d'imagerie moléculaire, radiothérapie et oncologie, UCL - SSS/IREC/CHEX - Pôle de chirgurgie expérimentale et transplantation, UCL - SSS/IREC/SLUC - Pôle St.-Luc, UCL - (SLuc) Service d'anatomie pathologique, UCL - (SLuc) Unité d'oncologie médicale, UCL - (SLuc) Service de chirurgie et transplantation abdominale, and UCL - (SLuc) Centre du cancer

Published
2016

33. Comprehensive Intrametastatic Immune Quantification and Major Impact of Immunoscore on Survival

Author

Mlecnik, Bernhard, primary, Van den Eynde, Marc, additional, Bindea, Gabriela, additional, Church, Sarah E, additional, Vasaturo, Angela, additional, Fredriksen, Tessa, additional, Lafontaine, Lucie, additional, Haicheur, Nacilla, additional, Marliot, Florence, additional, Debetancourt, Daphné, additional, Pairet, Géraldine, additional, Jouret-Mourin, Anne, additional, Gigot, Jean-Francois, additional, Hubert, Catherine, additional, Danse, Etienne, additional, Dragean, Cristina, additional, Carrasco, Javier, additional, Humblet, Yves, additional, Valge-Archer, Viia, additional, Berger, Anne, additional, Pagès, Franck, additional, Machiels, Jean-Pascal, additional, and Galon, Jérôme, additional

Published
2017
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34. Metastatic colorectal cancer has heterogeneous immune microenvironment and mutational expression

Author

UCL - SSS/IREC/GAEN - Pôle d'Hépato-gastro-entérologie, UCL - SSS/IREC/MIRO - Pôle d'imagerie moléculaire, radiothérapie et oncologie, UCL - SSS/IREC/CHEX - Pôle de chirgurgie expérimentale et transplantation, UCL - SSS/IREC/SLUC - Pôle St.-Luc, UCL - (SLuc) Service d'anatomie pathologique, UCL - (SLuc) Unité d'oncologie médicale, UCL - (SLuc) Service de chirurgie et transplantation abdominale, UCL - (SLuc) Centre du cancer, Van den Eynde, Marc, Mlecnik, Bernhard, Bindea, Gabriela, Fredriksen, Tessa, Lafontaine, Lucie, Haicheur, Nacilla, Marliot, Florence, Debetancourt, Daphné, Mourin, Anne, Sempoux, Christine, Gigot, Jean-François, Hubert, Catherine, Kartheuser, Alex, Remue, Christophe, Léonard, Daniel, Carrasco, Javier, Humblet, Yves, Pages, Franck, Machiels, Jean-Pascal, Galon, Jerome, Belgian Week of Gastroenterology - XXVIIIth edition, UCL - SSS/IREC/GAEN - Pôle d'Hépato-gastro-entérologie, UCL - SSS/IREC/MIRO - Pôle d'imagerie moléculaire, radiothérapie et oncologie, UCL - SSS/IREC/CHEX - Pôle de chirgurgie expérimentale et transplantation, UCL - SSS/IREC/SLUC - Pôle St.-Luc, UCL - (SLuc) Service d'anatomie pathologique, UCL - (SLuc) Unité d'oncologie médicale, UCL - (SLuc) Service de chirurgie et transplantation abdominale, UCL - (SLuc) Centre du cancer, Van den Eynde, Marc, Mlecnik, Bernhard, Bindea, Gabriela, Fredriksen, Tessa, Lafontaine, Lucie, Haicheur, Nacilla, Marliot, Florence, Debetancourt, Daphné, Mourin, Anne, Sempoux, Christine, Gigot, Jean-François, Hubert, Catherine, Kartheuser, Alex, Remue, Christophe, Léonard, Daniel, Carrasco, Javier, Humblet, Yves, Pages, Franck, Machiels, Jean-Pascal, Galon, Jerome, and Belgian Week of Gastroenterology - XXVIIIth edition

Published
2016

35. 31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016): late breaking abstracts

Author

Althammer, Sonja, primary, Steele, Keith, additional, Rebelatto, Marlon, additional, Tan, Tze Heng, additional, Wiestler, Tobias, additional, Schmidt, Guenter, additional, Higgs, Brandon, additional, Li, Xia, additional, Shi, Li, additional, Jin, Xiaoping, additional, Antal, Joyce, additional, Gupta, Ashok, additional, Ranade, Koustubh, additional, Binning, Gerd, additional, Bellmunt, Joaquim, additional, de Wit, Ronald, additional, Vaughn, David J., additional, Fradet, Yves, additional, Lee, Jae Lyun, additional, Fong, Lawrence, additional, Vogelzang, Nicholas J., additional, Climent, Miguel A., additional, Petrylak, Daniel P., additional, Choueiri, Toni K., additional, Necchi, Andrea, additional, Gerritsen, Winald, additional, Gurney, Howard, additional, Quinn, David I., additional, Culine, Stéphane, additional, Sternberg, Cora N., additional, Mai, Yabing, additional, Puhlmann, Markus, additional, Perini, Rodolfo F., additional, Bajorin, Dean F., additional, Sharma, Padmanee, additional, Callahan, Margaret K., additional, Calvo, Emiliano, additional, Kim, Joseph W., additional, de Braud, Filipo, additional, Ott, Patrick A., additional, Bono, Petri, additional, Pillai, Rathi N., additional, Morse, Michael, additional, Le, Dung T., additional, Taylor, Matthew, additional, Spilliopoulou, Pavlina, additional, Bendell, Johanna, additional, Jaeger, Dirk, additional, Chan, Emily, additional, Antonia, Scott J., additional, Ascierto, Paolo A., additional, Hennicken, Delphine, additional, Tschaika, Marina, additional, Azrilevich, Alex, additional, Rosenberg, Jonathan, additional, Levy, Ofer, additional, Chan, Christopher, additional, Cojocaru, Gady, additional, Liang, Spencer, additional, Ophir, Eran, additional, Ganguly, Sudipto, additional, Toporik, Amir, additional, Kotturi, Maya, additional, Kfir, Tal Fridman, additional, Murter, Benjamin M., additional, Logronio, Kathryn, additional, Dassa, Liat, additional, Leung, Ling, additional, Greenwald, Shirley, additional, Azulay, Meir, additional, Kumar, Sandeep, additional, Alteber, Zoya, additional, Pan, Xiaoyu, additional, Machlenkin, Arthur, additional, Benita, Yair, additional, Drake, Andrew W., additional, Chajut, Ayelet, additional, Salomon, Ran, additional, Vankin, Ilan, additional, Safyon, Einav, additional, Hunter, John, additional, Levine, Zurit, additional, White, Mark, additional, Leidner, Rom, additional, Kang, Hyunseok, additional, Haddad, Robert, additional, Segal, Neil H., additional, Wirth, Lori J., additional, Ferris, Robert L., additional, Hodi, F. Stephen, additional, Sanborn, Rachel E., additional, Gajewski, Thomas F., additional, Sharfman, William, additional, McDonald, Dan, additional, Srivastava, Shivani, additional, Gu, Xuemin, additional, Phillips, Penny, additional, Passey, Chaitali, additional, Seiwert, Tanguy, additional, Habtetsion, Tsadik, additional, Zhou, Gang, additional, Sakellariou-Thompson, Donastas, additional, Haymaker, Cara, additional, Creasy, Caitlin, additional, Hurd, Mark, additional, Uraoka, Naohiro, additional, Canales, Jaime Rodriguez, additional, Koptez, Scott, additional, Hwu, Patrick, additional, Maitra, Anirban, additional, Bernatchez, Chantale, additional, Coyle, Scott M., additional, Roybel, Kole T., additional, Rupp, Levi J., additional, Santoro, Stephen P., additional, Secrest, Stephanie, additional, Spelman, Michael, additional, Ho, Hanson, additional, Gomes, Tina, additional, Tse, Tiffany, additional, Yung-Wu, Chia, additional, Taunton, Jack, additional, Lim, Wendell, additional, Emtage, Peter, additional, Moudgil, Tarsem, additional, Ballesteros-Merino, Carmen, additional, Hilton, Traci, additional, Paustian, Christopher, additional, Page, David, additional, Urba, Walter, additional, Fox, Bernard, additional, Bell, Bryan, additional, Patel, Ashish, additional, Olafsen, Tove, additional, Satpayev, Daulet, additional, Torgov, Michael, additional, Marchioni, Filippo, additional, Romero, Jason, additional, Jiang, Ziyue Karen, additional, Zamilpa, Charles, additional, Keppler, Jennifer S., additional, Mascioni, Alessandro, additional, Jia, Fang, additional, Lee, Chen-Yu, additional, Gudas, Jean, additional, Sullivan, Ryan J., additional, Hoshida, Yujin, additional, Logan, Theodore, additional, Khushalani, Nikhil, additional, Giobbie-Hurder, Anita, additional, Margolin, Kim, additional, Roder, Joanna, additional, Bhatt, Rupal, additional, Koon, Henry, additional, Olencki, Thomas, additional, Hutson, Thomas, additional, Curti, Brendan, additional, Blackmon, Shauna, additional, Mier, James W., additional, Puzanov, Igor, additional, Roder, Heinrich, additional, Stewart, John, additional, Amin, Asim, additional, Ernstoff, Marc S., additional, Clark, Joseph I., additional, Atkins, Michael B., additional, Kaufman, Howard L., additional, Sosman, Jeffrey, additional, Signoretti, Sabina, additional, McDermott, David F., additional, Anderson, Abraham A., additional, Milhem, Mohammed M., additional, Andtbacka, Robert H. I., additional, Minor, David, additional, Gorski, Kevin S., additional, Baker, Daniel M., additional, Hamid, Omid, additional, Akporiaye, Emmanuel, additional, Koguchi, Yoshinobu, additional, Sutcliffe, Kim, additional, Conder, Kristie, additional, Marron, Thomas, additional, Bhardwaj, Nina, additional, Hammerich, Linda, additional, George, Fiby, additional, Kim-Schulze, Seunghee, additional, Keler, Tibor, additional, Davis, Tom, additional, Crowley, Elizabeth, additional, Salazar, Andres, additional, Brody, Joshua, additional, Monjazeb, Arta, additional, Daly, Megan E., additional, Riess, Jonathan, additional, Li, Tianhong, additional, Murphy, William J., additional, Kelly, Karen, additional, Hu, Zhiwei, additional, Shen, Rulong, additional, Campbell, Amanda, additional, McMichael, Elizabeth, additional, Yu, Lianbo, additional, Ramaswam, Bhuvaneswari, additional, London, Cheryl A., additional, Xu, Tian, additional, Carson, William, additional, Kokolus, Kathleen M., additional, Repasky, Elizabeth A., additional, Schell, Todd D., additional, Drabick, Joseph D., additional, Messenheimer, David J., additional, Jensen, Shawn, additional, Rubinstein, Mark, additional, Andrijauskaite, Kristina, additional, Swiderska-syn, Marzena, additional, Lind, Kristin, additional, Choppin, Agnes, additional, Roell, Marina K., additional, Wrangle, John, additional, Rhode, Peter, additional, Wong, Hing, additional, Ahmad, Shamim, additional, Webb, Mason, additional, Abu-Eid, Rasha, additional, Shrimali, Rajeev, additional, Verma, Vivek, additional, Doroodchi, Atbin, additional, Berrong, Zuzana, additional, Yashar, David, additional, Samara, Raed, additional, Mkrtichyan, Mikayel, additional, Khleif, Samir, additional, Powell, Steven, additional, Gitau, Mark, additional, Sumey, Christopher, additional, Terrell, Andrew, additional, Lohr, Michele, additional, Nowak, Ryan K., additional, McGraw, Steven, additional, Jensen, Ash, additional, Blanchard, Miran, additional, Gold, Kathryn A., additional, Cohen, Ezra E. W., additional, Ellison, Christie, additional, Black, Lora, additional, Lee, John, additional, Spanos, William Chad, additional, Wennerberg, Erik, additional, Schwitzer, Emily, additional, Lhuillier, Claire, additional, Koelwyn, Graeme, additional, Hiner, Rebecca, additional, Jones, Lee, additional, Demaria, Sandra, additional, Amanda, Vandeveer, additional, Greiner, John W., additional, Schlom, Jeffrey, additional, Bookstaver, Michelle, additional, Jewell, Christopher M., additional, Gunderson, Andrew, additional, Boulmay, Brian, additional, Li, Rui, additional, Spieler, Bradley, additional, Happel, Kyle, additional, Feng, Zipei, additional, Dubay, Christopher, additional, Fisher, Brenda, additional, Aung, Sandra, additional, Mederos, Eileen, additional, Bifulco, Carlo B., additional, McNamara, Michael, additional, Bahjat, Keith, additional, Redmond, William, additional, Ochoa, Augusto, additional, Hu, Hong-Ming, additional, Mehta, Adi, additional, Lund-Johansen, Fridtjof, additional, Bedu-Addo, Frank, additional, Conn, Greg, additional, King, Michael, additional, Dutta, Panna, additional, Shepard, Robert, additional, Einstein, Mark, additional, Adams, Sylvia, additional, Wang, Ena, additional, Jin, Ping, additional, Novik, Yelena, additional, Morrison, Debra, additional, Oratz, Ruth, additional, Marincola, Franco M., additional, Stroncek, David, additional, Goldberg, Judith, additional, Formenti, Silvia C., additional, Galon, Jérôme, additional, Mlecnik, Bernhard, additional, Marliot, Florence, additional, Ou, Fang-Shu, additional, Lugli, Alessandro, additional, Zlobec, Inti, additional, Rau, Tilman T., additional, Nagtegaal, Iris D., additional, Vink-Borger, Elisa, additional, Hartmann, Arndt, additional, Geppert, Carol, additional, Roehrl, Michael H., additional, Bavi, Prashant, additional, Ohashi, Pamela S., additional, Wang, Julia Y., additional, Nguyen, Linh T., additional, Han, SeongJun, additional, MacGregor, Heather L., additional, Hafezi-Bakhtiari, Sara, additional, Wouters, Bradley G., additional, Kawakami, Yutaka, additional, Papivanova, Boryana, additional, Xu, Mingli, additional, Fujita, Tomonobu, additional, Hazama, Shoichi, additional, Suzuki, Nobuaki, additional, Nagano, Hiroaki, additional, Okuno, Kiyotaka, additional, Itoh, Kyogo, additional, Zavadova, Eva, additional, Vocka, Michal, additional, Spacek, Jan, additional, Petruzelka, Lubos, additional, Konopasek, Bohuslav, additional, Dundr, Pavel, additional, Skalova, Helena, additional, Torigoe, Toshihiko, additional, Sato, Noriyuki, additional, Furuhata, Tomohisa, additional, Takemasa, Ichiro, additional, Van den Eynde, Marc, additional, Jouret-Mourin, Anne, additional, Machiels, Jean-Pascal, additional, Fredriksen, Tessa, additional, Lafontaine, Lucie, additional, Buttard, Bénédicte, additional, Church, Sarah, additional, Maby, Pauline, additional, Angell, Helen, additional, Angelova, Mihaela, additional, Vasaturo, Angela, additional, Bindea, Gabriela, additional, Berger, Anne, additional, Lagorce, Christine, additional, Patel, Prabhu S., additional, Vora, Hemangini H., additional, Shah, Birva, additional, Patel, Jayendrakumar B., additional, Rajvik, Kruti N., additional, Pandya, Shashank J., additional, Shukla, Shilin N., additional, Wang, Yili, additional, Zhang, Guanjun, additional, Masucci, Giuseppe V., additional, Andersson, Emilia K., additional, Grizzi, Fabio, additional, Laghi, Luigi, additional, Botti, Gerardo, additional, Tatangelo, Fabiana, additional, Delrio, Paolo, additional, Cilberto, Gennaro, additional, Marincola, Franco, additional, Sargent, Daniel J., additional, Fox, Bernard A., additional, Algazi, Alain, additional, Tsai, Katy, additional, Rosenblum, Michael, additional, Nandoskar, Prachi, additional, Li, Amy, additional, Nonomura, John, additional, Takamura, Kathryn, additional, Dwyer, Mary, additional, Browning, Erica, additional, Talia, Reneta, additional, Twitty, Chris, additional, Gargosky, Sharron, additional, Campbell, Jean, additional, Le, Mai, additional, Pierce, Robert H., additional, Daud, Adil, additional, Gartrell, Robyn, additional, Marks, Douglas, additional, Stack, Edward, additional, Lu, Yan, additional, Izaki, Daisuke, additional, Beck, Kristen, additional, Jia, Dan Tong, additional, Armenta, Paul, additional, White-Stern, Ashley, additional, Fu, Yichun, additional, Blake, Zoe, additional, Taback, Bret, additional, Horst, Basil, additional, Saenger, Yvonne M., additional, Leonardo, Steven, additional, Gorden, Keith, additional, Fulton, Ross B., additional, Fraser, Kathryn, additional, Kangas, Takashi O., additional, Walsh, Richard, additional, Ertelt, Kathleen, additional, Graff, Jeremy, additional, Uhlik, Mark, additional, Sims, Jennifer S., additional, Lei, Liang, additional, Tsujiuchi, Takashi, additional, Bruce, Jeffrey N., additional, Canoll, Peter, additional, Tolcher, Anthony W, additional, Alley, Evan W, additional, Chichili, Gurunadh, additional, Canoll, Jan E, additional, Moore, Paul, additional, Bonvini, Ezio, additional, Johnson, Syd, additional, Shankar, Sadhna, additional, Vasselli, James, additional, Wigginton, Jon, additional, and Powderly, John, additional

Published
2016
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36. The tumor microenvironment and Immunoscore are critical determinants of dissemination to distant metastasis

Author

Mlecnik, Bernhard, primary, Bindea, Gabriela, additional, Kirilovsky, Amos, additional, Angell, Helen K., additional, Obenauf, Anna C., additional, Tosolini, Marie, additional, Church, Sarah E., additional, Maby, Pauline, additional, Vasaturo, Angela, additional, Angelova, Mihaela, additional, Fredriksen, Tessa, additional, Mauger, Stéphanie, additional, Waldner, Maximilian, additional, Berger, Anne, additional, Speicher, Michael R., additional, Pagès, Franck, additional, Valge-Archer, Viia, additional, and Galon, Jérôme, additional

Published
2016
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37. Abstract A114: Towards personalized cellular adoptive immunotherapy targeting tumor specific neo-antigens in microsatellite unstable colorectal cancers

Author

Maby, Pauline, primary, Hamieh, Mohamad, additional, Kora, Hafid, additional, Tougeron, David, additional, Mlecnik, Bernhard, additional, Bindea, Gabriela, additional, Angell, Helen K., additional, Fredriksen, Tessa, additional, Elie, Nicolas, additional, Fauquembergue, Emilie, additional, Drouet, Aurélie, additional, Leprince, Jérôme, additional, Benichou, Jacques, additional, Mauillon, Jacques, additional, Pessot, Florence Le, additional, Sesboüé, Richard, additional, Frébourg, Thierry, additional, Galon, Jérôme, additional, and Latouche, Jean-Baptiste, additional

Published
2016
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38. Comprehensive Intrametastatic Immune Quantification and Major Impact of Immunoscore on Survival.

Author

Mlecnik, Bernhard, Van den Eynde, Marc, Bindea, Gabriela, Church, Sarah E., Vasaturo, Angela, Fredriksen, Tessa, Lafontaine, Lucie, Haicheur, Nacilla, Marliot, Florence, Debetancourt, Daphné, Pairet, Géraldine, Jouret-Mourin, Anne, Gigot, Jean-Francois, Hubert, Catherine, Danse, Etienne, Dragean, Cristina, Carrasco, Javier, Humblet, Yves, Valge-Archer, Viia, and Berger, Anne

Subjects
ANTIGEN analysis, ANTINEOPLASTIC agents, PROTEIN analysis, TREATMENT of lung tumors, B cells, ONCOLOGIC surgery, CELL physiology, COLON tumors, COMBINED modality therapy, HEPATECTOMY, LIVER tumors, LONGITUDINAL method, LUNG tumors, LYMPHOCYTES, METASTASIS, PNEUMONECTOMY, PROGNOSIS, SURVIVAL, RECTUM tumors, T cells, CANCER treatment, TREATMENT effectiveness, PREOPERATIVE period, LYMPHOCYTE count, TUMOR treatment
Abstract

Background: This study assesses how the metastatic immune landscape is impacting the response to treatment and the outcome of colorectal cancer (CRC) patients.Methods: Complete curative resection of metastases (n = 441) was performed for two patient cohorts (n = 153). Immune densities were quantified in the center and invasive margin of all metastases. Immunoscore and T and B cell (TB) score were analyzed in relation to radiological and pathological responses and patient's disease-free (DFS) and overall survival (OS) using multivariable Cox proportional hazards models. All statistical tests were two-sided.Results: The spatial distribution of immune cells within metastases was nonuniform. Patients, as well as metastases of the same patient, had variable immune infiltrates and response to therapy. A beneficial response was statistically significantly associated with increased immune densities. Among all metastases, Immunoscore (I) and TB score evaluated in the least immune-infiltrated metastases were the strongest predictors for DFS and OS (five-year follow-up, Immunoscore: I 3-4: DFS rate = 27.9%, 95% CI = 15.2 to 51.3; vs I 0-1-2: DFS rate = 12.3%, 95% CI = 4.9 to 30.6; HR = 0.45, 95% CI = 0.28 to 0.70, P = .02; I 3-4: OS rate = 64.6%, 95% CI = 46.6 to 89.6; vs I 0-1-2: OS rate = 32.5%, 95% CI = 17.2 to 61.4; HR = 0.32, 95% CI = 0.15 to 0.66, P = .001, C-index = 65.9%; five-year follow-up, TB score: TB 3-4: DFS rate = 25.7%, 95% CI = 14.2 to 46.6; vs TB 0-1-2: DFS rate = 5.0%, 95% CI = 0.8 to 32.4; HR = 0.36, 95% CI = 0.22 to 0.57, P < .001; TB 3-4: OS rate = 63.7%, 95% CI = 46.4 to 87.5; vs TB 0-1-2: OS rate: 21.4%, 95% CI = 9.2 to 49.8; HR = 0.25, 95% CI = 0.12 to 0.51, P < .001, C-index = 67.8%). High TB score and Immunoscore patients had a median survival of 70.5 months, while low patients survived only 25.1 to 38.3 months. Nonresponding patients with high-immune infiltrates had prolonged DFS (HR = 0.28, 95% CI = 0.15 to 0.52, P = .001) and OS (HR = 0.25, 95% CI = 0.1 to 0.62, P = .001). The immune parameters remained the only statistically significant prognostic factor associated with DFS and OS in multivariable analysis (P < .001), while response to treatment was not.Conclusions: Response to treatment and prolonged survival of metastatic CRC patients were statistically significantly associated with high-immune densities quantified into the least immune-infiltrated metastasis. [ABSTRACT FROM AUTHOR]

Published
2018
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39. Correlation between Density of CD8+ T-cell Infiltrate in Microsatellite Unstable Colorectal Cancers and Frameshift Mutations: A Rationale for Personalized Immunotherapy

Author

Maby, Pauline, primary, Tougeron, David, additional, Hamieh, Mohamad, additional, Mlecnik, Bernhard, additional, Kora, Hafid, additional, Bindea, Gabriela, additional, Angell, Helen K., additional, Fredriksen, Tessa, additional, Elie, Nicolas, additional, Fauquembergue, Emilie, additional, Drouet, Aurélie, additional, Leprince, Jérôme, additional, Benichou, Jacques, additional, Mauillon, Jacques, additional, Le Pessot, Florence, additional, Sesboüé, Richard, additional, Tuech, Jean-Jacques, additional, Sabourin, Jean-Christophe, additional, Michel, Pierre, additional, Frébourg, Thierry, additional, Galon, Jérôme, additional, and Latouche, Jean-Baptiste, additional

Published
2015
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41. Clinical Impact of Different Classes of Infiltrating T Cytotoxic and Helper Cells (Th1, Th2, Treg, Th17) in Patients with Colorectal Cancer

Author

Tosolini, Marie, primary, Kirilovsky, Amos, additional, Mlecnik, Bernhard, additional, Fredriksen, Tessa, additional, Mauger, Stéphanie, additional, Bindea, Gabriela, additional, Berger, Anne, additional, Bruneval, Patrick, additional, Fridman, Wolf-Herman, additional, Pagès, Franck, additional, and Galon, Jérôme, additional

Published
2011
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42. TCF4Deletions in Pitt-Hopkins Syndrome

Author

Giurgea, Irina, primary, Missirian, Chantal, additional, Cacciagli, Pierre, additional, Whalen, Sandra, additional, Fredriksen, Tessa, additional, Gaillon, Thierry, additional, Rankin, Julia, additional, Mathieu-Dramard, Michele, additional, Morin, Gilles, additional, Martin-Coignard, Dominique, additional, Dubourg, Christèle, additional, Chabrol, Brigitte, additional, Arfi, Jacqueline, additional, Giuliano, Fabienne, additional, Claude Lambert, Jean, additional, Philip, Nicole, additional, Sarda, Pierre, additional, Villard, Laurent, additional, Goossens, Michel, additional, and Moncla, Anne, additional

Published
2008
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43. Functional Network Pipeline Reveals Genetic Determinants Associated with in Situ Lymphocyte Proliferation and Survival of Cancer Patients.

Author

Mlecnik, Bernhard, Bindea, Gabriela, Angel, Helen K., Sasso, Maria Stella, Obenauf, Anna C., Fredriksen, Tessa, Lafontaine, Lucie, Bilocq, Amelie M., Kirilovsky, Amos, Tosolini, Marie, Waldner, Maximilian, Berger, Anne, Fridman, Wolf Herman, Rafii, Arash, Valge-Archer, Viia, Pagès, Franck, Speicher, Michael R., and Galon, Jérôme

Published
2014
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44. 31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016): late breaking abstracts

Author

Althammer, Sonja, Steele, Keith, Rebelatto, Marlon, Tan, Tze Heng, Wiestler, Tobias, Schmidt, Guenter, Higgs, Brandon, Li, Xia, Shi, Li, Jin, Xiaoping, Antal, Joyce, Gupta, Ashok, Ranade, Koustubh, Binning, Gerd, Bellmunt, Joaquim, de Wit, Ronald, Vaughn, David J., Fradet, Yves, Lee, Jae Lyun, Fong, Lawrence, Vogelzang, Nicholas J., Climent, Miguel A., Petrylak, Daniel P., Choueiri, Toni K., Necchi, Andrea, Gerritsen, Winald, Gurney, Howard, Quinn, David I., Culine, Stéphane, Sternberg, Cora N., Mai, Yabing, Puhlmann, Markus, Perini, Rodolfo F., Bajorin, Dean F., Sharma, Padmanee, Callahan, Margaret K., Calvo, Emiliano, Kim, Joseph W., de Braud, Filipo, Ott, Patrick A., Bono, Petri, Pillai, Rathi N., Morse, Michael, Le, Dung T., Taylor, Matthew, Spilliopoulou, Pavlina, Bendell, Johanna, Jaeger, Dirk, Chan, Emily, Antonia, Scott J., Ascierto, Paolo A., Hennicken, Delphine, Tschaika, Marina, Azrilevich, Alex, Rosenberg, Jonathan, Levy, Ofer, Chan, Christopher, Cojocaru, Gady, Liang, Spencer, Ophir, Eran, Ganguly, Sudipto, Toporik, Amir, Kotturi, Maya, Kfir, Tal Fridman, Murter, Benjamin M., Logronio, Kathryn, Dassa, Liat, Leung, Ling, Greenwald, Shirley, Azulay, Meir, Kumar, Sandeep, Alteber, Zoya, Pan, Xiaoyu, Machlenkin, Arthur, Benita, Yair, Drake, Andrew W., Chajut, Ayelet, Salomon, Ran, Vankin, Ilan, Safyon, Einav, Hunter, John, Levine, Zurit, White, Mark, Leidner, Rom, Kang, Hyunseok, Haddad, Robert, Segal, Neil H., Wirth, Lori J., Ferris, Robert L., Hodi, F. Stephen, Sanborn, Rachel E., Gajewski, Thomas F., Sharfman, William, McDonald, Dan, Srivastava, Shivani, Gu, Xuemin, Phillips, Penny, Passey, Chaitali, Seiwert, Tanguy, Habtetsion, Tsadik, Zhou, Gang, Sakellariou-Thompson, Donastas, Haymaker, Cara, Creasy, Caitlin, Hurd, Mark, Uraoka, Naohiro, Canales, Jaime Rodriguez, Koptez, Scott, Hwu, Patrick, Maitra, Anirban, Bernatchez, Chantale, Coyle, Scott M., Roybel, Kole T., Rupp, Levi J., Santoro, Stephen P., Secrest, Stephanie, Spelman, Michael, Ho, Hanson, Gomes, Tina, Tse, Tiffany, Yung-Wu, Chia, Taunton, Jack, Lim, Wendell, Emtage, Peter, Moudgil, Tarsem, Ballesteros-Merino, Carmen, Hilton, Traci, Paustian, Christopher, Page, David, Urba, Walter, Fox, Bernard, Bell, Bryan, Patel, Ashish, Olafsen, Tove, Satpayev, Daulet, Torgov, Michael, Marchioni, Filippo, Romero, Jason, Jiang, Ziyue Karen, Zamilpa, Charles, Keppler, Jennifer S., Mascioni, Alessandro, Jia, Fang, Lee, Chen-Yu, Gudas, Jean, Sullivan, Ryan J., Hoshida, Yujin, Logan, Theodore, Khushalani, Nikhil, Giobbie-Hurder, Anita, Margolin, Kim, Roder, Joanna, Bhatt, Rupal, Koon, Henry, Olencki, Thomas, Hutson, Thomas, Curti, Brendan, Blackmon, Shauna, Mier, James W., Puzanov, Igor, Roder, Heinrich, Stewart, John, Amin, Asim, Ernstoff, Marc S., Clark, Joseph I., Atkins, Michael B., Kaufman, Howard L., Sosman, Jeffrey, Signoretti, Sabina, McDermott, David F., Anderson, Abraham A., Milhem, Mohammed M., Andtbacka, Robert H. I., Minor, David, Gorski, Kevin S., Baker, Daniel M., Hamid, Omid, Akporiaye, Emmanuel, Koguchi, Yoshinobu, Sutcliffe, Kim, Conder, Kristie, Marron, Thomas, Bhardwaj, Nina, Hammerich, Linda, George, Fiby, Kim-Schulze, Seunghee, Keler, Tibor, Davis, Tom, Crowley, Elizabeth, Salazar, Andres, Brody, Joshua, Monjazeb, Arta, Daly, Megan E., Riess, Jonathan, Li, Tianhong, Murphy, William J., Kelly, Karen, Hu, Zhiwei, Shen, Rulong, Campbell, Amanda, McMichael, Elizabeth, Yu, Lianbo, Ramaswam, Bhuvaneswari, London, Cheryl A., Xu, Tian, Carson, William, Kokolus, Kathleen M., Repasky, Elizabeth A., Schell, Todd D., Drabick, Joseph D., Messenheimer, David J., Jensen, Shawn, Rubinstein, Mark, Andrijauskaite, Kristina, Swiderska-syn, Marzena, Lind, Kristin, Choppin, Agnes, Roell, Marina K., Wrangle, John, Rhode, Peter, Wong, Hing, Ahmad, Shamim, Webb, Mason, Abu-Eid, Rasha, Shrimali, Rajeev, Verma, Vivek, Doroodchi, Atbin, Berrong, Zuzana, Yashar, David, Samara, Raed, Mkrtichyan, Mikayel, Khleif, Samir, Powell, Steven, Gitau, Mark, Sumey, Christopher, Terrell, Andrew, Lohr, Michele, Nowak, Ryan K., McGraw, Steven, Jensen, Ash, Blanchard, Miran, Gold, Kathryn A., Cohen, Ezra E. W., Ellison, Christie, Black, Lora, Lee, John, Spanos, William Chad, Wennerberg, Erik, Schwitzer, Emily, Lhuillier, Claire, Koelwyn, Graeme, Hiner, Rebecca, Jones, Lee, Demaria, Sandra, Amanda, Vandeveer, Greiner, John W., Schlom, Jeffrey, Bookstaver, Michelle, Jewell, Christopher M., Gunderson, Andrew, Boulmay, Brian, Li, Rui, Spieler, Bradley, Happel, Kyle, Feng, Zipei, Dubay, Christopher, Fisher, Brenda, Aung, Sandra, Mederos, Eileen, Bifulco, Carlo B., McNamara, Michael, Bahjat, Keith, Redmond, William, Ochoa, Augusto, Hu, Hong-Ming, Mehta, Adi, Lund-Johansen, Fridtjof, Bedu-Addo, Frank, Conn, Greg, King, Michael, Dutta, Panna, Shepard, Robert, Einstein, Mark, Adams, Sylvia, Wang, Ena, Jin, Ping, Novik, Yelena, Morrison, Debra, Oratz, Ruth, Marincola, Franco M., Stroncek, David, Goldberg, Judith, Formenti, Silvia C., Galon, Jérôme, Mlecnik, Bernhard, Marliot, Florence, Ou, Fang-Shu, Lugli, Alessandro, Zlobec, Inti, Rau, Tilman T., Nagtegaal, Iris D., Vink-Borger, Elisa, Hartmann, Arndt, Geppert, Carol, Roehrl, Michael H., Bavi, Prashant, Ohashi, Pamela S., Wang, Julia Y., Nguyen, Linh T., Han, SeongJun, MacGregor, Heather L., Hafezi-Bakhtiari, Sara, Wouters, Bradley G., Kawakami, Yutaka, Papivanova, Boryana, Xu, Mingli, Fujita, Tomonobu, Hazama, Shoichi, Suzuki, Nobuaki, Nagano, Hiroaki, Okuno, Kiyotaka, Itoh, Kyogo, Zavadova, Eva, Vocka, Michal, Spacek, Jan, Petruzelka, Lubos, Konopasek, Bohuslav, Dundr, Pavel, Skalova, Helena, Torigoe, Toshihiko, Sato, Noriyuki, Furuhata, Tomohisa, Takemasa, Ichiro, Van den Eynde, Marc, Jouret-Mourin, Anne, Machiels, Jean-Pascal, Fredriksen, Tessa, Lafontaine, Lucie, Buttard, Bénédicte, Church, Sarah, Maby, Pauline, Angell, Helen, Angelova, Mihaela, Vasaturo, Angela, Bindea, Gabriela, Berger, Anne, Lagorce, Christine, Patel, Prabhu S., Vora, Hemangini H., Shah, Birva, Patel, Jayendrakumar B., Rajvik, Kruti N., Pandya, Shashank J., Shukla, Shilin N., Wang, Yili, Zhang, Guanjun, Masucci, Giuseppe V., Andersson, Emilia K., Grizzi, Fabio, Laghi, Luigi, Botti, Gerardo, Tatangelo, Fabiana, Delrio, Paolo, Cilberto, Gennaro, Marincola, Franco, Sargent, Daniel J., Fox, Bernard A., Algazi, Alain, Tsai, Katy, Rosenblum, Michael, Nandoskar, Prachi, Li, Amy, Nonomura, John, Takamura, Kathryn, Dwyer, Mary, Browning, Erica, Talia, Reneta, Twitty, Chris, Gargosky, Sharron, Campbell, Jean, Le, Mai, Pierce, Robert H., Daud, Adil, Gartrell, Robyn, Marks, Douglas, Stack, Edward, Lu, Yan, Izaki, Daisuke, Beck, Kristen, Jia, Dan Tong, Armenta, Paul, White-Stern, Ashley, Fu, Yichun, Blake, Zoe, Taback, Bret, Horst, Basil, Saenger, Yvonne M., Leonardo, Steven, Gorden, Keith, Fulton, Ross B., Fraser, Kathryn, Kangas, Takashi O., Walsh, Richard, Ertelt, Kathleen, Graff, Jeremy, Uhlik, Mark, Sims, Jennifer S., Lei, Liang, Tsujiuchi, Takashi, Bruce, Jeffrey N., Canoll, Peter, Tolcher, Anthony W, Alley, Evan W, Chichili, Gurunadh, Canoll, Jan E, Moore, Paul, Bonvini, Ezio, Johnson, Syd, Shankar, Sadhna, Vasselli, James, Wigginton, Jon, and Powderly, John

Subjects
Meeting Abstracts
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45. Correlation between Density of CD8+ T-cell Infiltrate in Microsatellite Unstable Colorectal Cancers and Frameshift Mutations: A Rationale for Personalized Immunotherapy.

Author

Maby, Pauline, Tougeron, David, Hamieh, Mohamad, Mlecnik, Bernhard, Kora, Hafid, Bindea, Gabriela, Angell, Helen K., Fredriksen, Tessa, Elie, Nicolas, Fauquembergue, Emilie, Drouet, Aurélie, Leprince, Jérôme, Benichou, Jacques, Mauillon, Jacques, Le Pessot, Florence, Sesboüé, Richard, Tuech, Jean-Jacques, Sabourin, Jean-Christophe, Michel, Pierre, and Frébourg, Thierry

Subjects
*GENETICS of colon cancer, *MICROSATELLITE repeats, *HEREDITARY nonpolyposis colorectal cancer, *IMMUNOTHERAPY, *CLINICAL immunology
Abstract

Colorectal cancers with microsatellite instability (MSI) represent 15% of all colorectal cancers, including Lynch syndrome as the most frequent hereditary form of this disease. Notably, MSI colorectal cancers have a higher density of tumor-infiltrating lymphocytes (TIL) than other colorectal cancers. This feature is thought to reflect the accumulation of frameshift mutations in sequences that are repeated within gene coding regions, thereby leading to the synthesis of neoantigens recognized by CD8+ T cells. However, there has yet to be a clear link established between CD8+ TIL density and frameshift mutations in colorectal cancer. In this study, we examined this link in 103 MSI colorectal cancers from two independent cohorts where frameshift mutations in 19 genes were analyzed and CD3+, CD8+, and FOXP3+ TIL densities were quantitated. We found that CD8+ TIL density correlated positively with the total number of frameshift mutations. TIL densities increased when frameshiftmutations were present within the ASTE1, HNF1A, or TCF7L2 genes, increasing even further when at least one of these frameshift mutations was present in all tumor cells. Through in vitro assays using engineered antigen-presenting cells, we were able to stimulate peripheral cytotoxic T cells obtained from colorectal cancer patients with peptides derived from frameshift mutations found in their tumors. Taken together, our results highlight the importance of a CD8+ T cell immuneresponseagainstMSI colorectal cancer-specificneoantigens, establishing a preclinical rationale to target them as a personalized cellular immunotherapy strategy, an especially appealing goal for patients with Lynch syndrome. [ABSTRACT FROM AUTHOR]

Published
2015
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46. Evolution of Metastases in Space and Time under Immune Selection

Author

Gabriela Bindea, Lucie Lafontaine, Yves Humblet, Anne Jouret-Mourin, Najeeb Syed, Catherine Hubert, Alex Kartheuser, Mihaela Angelova, Daniela Bruni, Jérôme Galon, Michele Ceccarelli, Davide Bedognetti, Marc Van den Eynde, Bénédicte Buttard, Bernhard Mlecnik, Angela Vasaturo, Francesco M. Marincola, Erwan Morgand, Tessa Fredriksen, Angelova, Mihaela, Mlecnik, Bernhard, Vasaturo, Angela, Bindea, Gabriela, Fredriksen, Tessa, Lafontaine, Lucie, Buttard, Bénédicte, Morgand, Erwan, Bruni, Daniela, Jouret-Mourin, Anne, Hubert, Catherine, Kartheuser, Alex, Humblet, Yve, Ceccarelli, Michele, Syed, Najeeb, Marincola, Francesco M., Bedognetti, Davide, Van den Eynde, Marc, and Galon, Jérôme

Subjects
0301 basic medicine, Genetics and Molecular Biology (all), recurrence, Colorectal cancer, CD3, medicine.medical_treatment, immunoscore, Somatic evolution in cancer, Biochemistry, General Biochemistry, Genetics and Molecular Biology, Metastasis, immunoediting, 03 medical and health sciences, clonal, 0302 clinical medicine, Immune system, Lymphocytes, Tumor-Infiltrating, Leukemic Infiltration, Neoplasms, medicine, Tumor Microenvironment, Humans, Neoplasm Metastasis, Models, Statistical, biology, Cancer, T cell, Immunotherapy, medicine.disease, microenvironment, Tumor Burden, 030104 developmental biology, Immunoediting, 030220 oncology & carcinogenesis, Cancer research, biology.protein, metastasi, immunotherapy, heterogeneity, mutation
Abstract

We examined how the immune microenvironment molds tumor evolution at different metastatic organs in a longitudinal dataset of colorectal cancer. Through multiplexed analyses, we showed that clonal evolution patterns during metastatic progression depend on the immune contexture at the metastatic site. Genetic evidence of neoantigen depletion was observed in the sites with high Immunoscore and spatial proximity between Ki67+ tumor cells and CD3+ cells. The immunoedited tumor clones were eliminated and did not recur, while progressing clones were immune privileged, despite the presence of tumor-infiltrating lymphocytes. Characterization of immune-privileged metastases revealed tumor-intrinsic and tumor-extrinsic mechanisms of escape. The lowest recurrence risk was associated with high Immunoscore, occurrence of immunoediting, and low tumor burden. We propose a parallel selection model of metastatic progression, where branched evolution could be traced back to immune-escaping clones. The findings could inform the understanding of cancer dissemination and the development of immunotherapeutics.

Published
2018

47. Comprehensive Intrametastatic Immune Quantification and Major Impact of Immunoscore on Survival.

Author

Mlecnik B, Van den Eynde M, Bindea G, Church SE, Vasaturo A, Fredriksen T, Lafontaine L, Haicheur N, Marliot F, Debetancourt D, Pairet G, Jouret-Mourin A, Gigot JF, Hubert C, Danse E, Dragean C, Carrasco J, Humblet Y, Valge-Archer V, Berger A, Pagès F, Machiels JP, and Galon J

Subjects
Aged, Antigens, CD20 analysis, Antineoplastic Combined Chemotherapy Protocols therapeutic use, CD3 Complex analysis, CD8-Positive T-Lymphocytes, Chemotherapy, Adjuvant, Colorectal Neoplasms pathology, Colorectal Neoplasms therapy, Disease-Free Survival, Follow-Up Studies, Forkhead Transcription Factors analysis, Hepatectomy, Humans, Leukocyte Common Antigens analysis, Liver Neoplasms secondary, Liver Neoplasms therapy, Lung Neoplasms secondary, Lung Neoplasms therapy, Lymphocyte Count, Metastasectomy, Middle Aged, Neoplasm Metastasis, Pneumonectomy, Preoperative Period, Response Evaluation Criteria in Solid Tumors, Survival Rate, Tumor Microenvironment immunology, B-Lymphocytes chemistry, Colorectal Neoplasms immunology, Liver Neoplasms immunology, Lung Neoplasms immunology, Lymphocytes, Tumor-Infiltrating, T-Lymphocytes chemistry
Abstract

Background: This study assesses how the metastatic immune landscape is impacting the response to treatment and the outcome of colorectal cancer (CRC) patients., Methods: Complete curative resection of metastases (n = 441) was performed for two patient cohorts (n = 153). Immune densities were quantified in the center and invasive margin of all metastases. Immunoscore and T and B cell (TB) score were analyzed in relation to radiological and pathological responses and patient's disease-free (DFS) and overall survival (OS) using multivariable Cox proportional hazards models. All statistical tests were two-sided., Results: The spatial distribution of immune cells within metastases was nonuniform. Patients, as well as metastases of the same patient, had variable immune infiltrates and response to therapy. A beneficial response was statistically significantly associated with increased immune densities. Among all metastases, Immunoscore (I) and TB score evaluated in the least immune-infiltrated metastases were the strongest predictors for DFS and OS (five-year follow-up, Immunoscore: I 3-4: DFS rate = 27.9%, 95% CI = 15.2 to 51.3; vs I 0-1-2: DFS rate = 12.3%, 95% CI = 4.9 to 30.6; HR = 0.45, 95% CI = 0.28 to 0.70, P = .02; I 3-4: OS rate = 64.6%, 95% CI = 46.6 to 89.6; vs I 0-1-2: OS rate = 32.5%, 95% CI = 17.2 to 61.4; HR = 0.32, 95% CI = 0.15 to 0.66, P = .001, C-index = 65.9%; five-year follow-up, TB score: TB 3-4: DFS rate = 25.7%, 95% CI = 14.2 to 46.6; vs TB 0-1-2: DFS rate = 5.0%, 95% CI = 0.8 to 32.4; HR = 0.36, 95% CI = 0.22 to 0.57, P < .001; TB 3-4: OS rate = 63.7%, 95% CI = 46.4 to 87.5; vs TB 0-1-2: OS rate: 21.4%, 95% CI = 9.2 to 49.8; HR = 0.25, 95% CI = 0.12 to 0.51, P < .001, C-index = 67.8%). High TB score and Immunoscore patients had a median survival of 70.5 months, while low patients survived only 25.1 to 38.3 months. Nonresponding patients with high-immune infiltrates had prolonged DFS (HR = 0.28, 95% CI = 0.15 to 0.52, P = .001) and OS (HR = 0.25, 95% CI = 0.1 to 0.62, P = .001). The immune parameters remained the only statistically significant prognostic factor associated with DFS and OS in multivariable analysis (P < .001), while response to treatment was not., Conclusions: Response to treatment and prolonged survival of metastatic CRC patients were statistically significantly associated with high-immune densities quantified into the least immune-infiltrated metastasis., (© The Author 2017. Published by Oxford University Press.)

Published
2018
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