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2. Bimodal Effect of NKG2A Blockade on Intratumoral and Systemic CD8 T Cell Response Induced by Cancer Vaccine.

Author

Riva, Erika, Carboni, Susanna, di Berardino-Besson, Wilma, Moyat, Mati, Belnoue, Elodie, Devy-Dimanche, Laetitia, and Rossi, Matteo

Subjects
*T cells, *CANCER vaccines, *IMMUNE checkpoint inhibitors, *MICE, *ANIMAL experimentation, *DRUG efficacy, *TUMORS, *SURVIVAL analysis (Biometry), *CELL receptors
Abstract

Simple Summary: Combination therapy represents an important approach for the treatment of several types of cancer. We have previously shown that heterologous prime-boost vaccination with a protein-based cancer vaccine in combination with an oncolytic virus result in improved tumor growth control and deep remodeling of the tumor microenvironment. Here, we describe the impact of the immune-checkpoint inhibitor anti-NKG2A on tumor specific immune response induced by therapeutic vaccination in mouse tumor models. We show that NKG2A blockade has a bimodal effect on cancer vaccine induced T cell response, reducing the exhaustion of tumor infiltrating antigen-specific CD8 T cells, leading to an improved antitumoral efficacy, and at the same time influencing the establishment of systemic long-term immunological memory. Our data highlight the importance of considering the diverse impact of immunotherapy on systemic and intratumoral compartments, therefore potentially influencing the clinical outcome. Immune check-point blockade (ICB) has revitalized cancer immunotherapy, showing unprecedented efficacy despite only a narrow number of indications and with limited long-term protection. Cancer vaccines are promising combination partners for ICB to widen the patient population profiting from these treatments. Therapeutic heterologous prime-boost vaccination with KISIMATM protein vaccine and VSV-GP-TAg oncolytic virus was shown to inflame the tumor microenvironment, promoting significant infiltration of antigen-specific CD8 T cells resulting in robust antitumoral efficacy in mouse tumor models, and clinical trials are currently ongoing. Here, we report the impact of NKG2A blockade on antitumoral CD8 T cell immune response elicited by KISIMA—VSV-GP-TAg vaccination in tumor mouse models. Combination therapy significantly reduced the amount of vaccine-induced exhausted CD8 T cells infiltrating the tumor, resulting in short-term improved tumor growth control and prolonged mouse survival, while it also influenced the establishment of systemic effector memory CD8 T cell response. Taken together, these data show a compartment-dependent effect of NKG2A blockade on cancer vaccine-induced T cell immunity, increasing intratumoral T cell efficacy and attenuating the development of peripheral effector memory CD8 T cell response. [ABSTRACT FROM AUTHOR]

Published
2024
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6. Demographic, clinical, and service-use characteristics related to the clinician’s recommendation to transition from child to adult mental health services

Author

Gerritsen, S. E., van Bodegom, L. S., Dieleman, G. C., Overbeek, M. M., Verhulst, F. C., Wolke, Dieter, Rizopoulos, D., Appleton, R., van Amelsvoort, T. A. M. J., Bodier Rethore, C., Bonnet-Brilhault, F., Charvin, I., Da Fonseca, D., Davidović, N., Dodig-Ćurković, K., Ferrari, A., Fiori, F., Franić, T., Gatherer, C., de Girolamo, G., Heaney, N., Hendrickx, G., Jardri, R., Kolozsvari, A., Lida-Pulik, H., Lievesley, K., Madan, J., Mastroianni, M., Maurice, V., McNicholas, F., Nacinovich, R., Parenti, A., Paul, M., Purper-Ouakil, D., Rivolta, L., de Roeck, V., Russet, F., Saam, M. C., Sagar-Ouriaghli, I., Santosh, P. J., Sartor, A., Schulze, U. M. E., Scocco, P., Signorini, G., Singh, S. P., Singh, J., Speranza, M., Stagi, P., Stagni, P., Street, C., Tah, P., Tanase, E., Tremmery, S., Tuffrey, A., Tuomainen, H., Walker, L., Wilson, A., Maras, A., Adams, Laura, Allibrio, Giovanni, Armando, Marco, Aslan, Sonja, Baccanelli, Nadia, Balaudo, Monica, Bergamo, Fabia, Bertani, Angelo, Berriman, Jo, Boon, Albert, Braamse, Karen, Breuninger, Ulrike, Buttiglione, Maura, Buttle, Sarah, Schandrin, Aurélie, Cammarano, Marco, Canaway, Alastair, Cantini, Fortunata, Cappellari, Cristiano, Carenini, Marta, Carrà, Giuseppe, Ferrari, Cecilia, Chianura, Krizia, Coleman, Philippa, Colonna, Annalisa, Conese, Patrizia, Costanzo, Raffaella, Daffern, Claire, Danckaerts, Marina, de Giacomo, Andrea, Ermans, Jean-Pierre, Farmer, Alan, Fegert, Jörg M., Ferrari, Sabrina, Galea, Giuliana, Gatta, Michela, Gheza, Elisa, Goglia, Giacomo, Grandetto, MariaRosa, Griffin, James, Levi, Flavia Micol, Humbertclaude, Véronique, Ingravallo, Nicola, Invernizzi, Roberta, Kelly, Caoimhe, Killilea, Meghan, Kirwan, James, Klockaerts, Catherine, Kovač, Vlatka, Liew, Ashley, Lippens, Christel, Macchi, Francesca, Manenti, Lidia, Margari, Francesco, Margari, Lucia, Martinelli, Paola, McFadden, Leighton, Menghini, Deny, Miller, Sarah, Monzani, Emiliano, Morini, Giorgia, Mutafov, Todor, O’Hara, Lesley, Negrinotti, Cristina, Nelis, Emmanuel, Neri, Francesca, Nikolova, Paulina, Nossa, Marzia, Cataldo, Maria Giulia, Noterdaeme, Michele, Operto, Francesca, Panaro, Vittoria, Pastore, Adriana, Pemmaraju, Vinuthna, Pepermans, Ann, Petruzzelli, Maria Giuseppina, Presicci, Anna, Prigent, Catherine, Rinaldi, Francesco, Riva, Erika, Roekens, Anne, Rogers, Ben, Ronzini, Pablo, Sakar, Vehbi, Salvetti, Selena, Martinelli, Ottaviano, Sandhu, Tanveer, Schepker, Renate, Siviero, Marco, Slowik, Michael, Smyth, Courtney, Conti, Patrizia, Spadone, Maria Antonietta, Starace, Fabrizio, Stoppa, Patrizia, Tansini, Lucia, Toselli, Cecilia, Trabucchi, Guido, Tubito, Maria, van Dam, Arno, van Gutschoven, Hanne, van West, Dirk, Vanni, Fabio, Vannicola, Chiara, Varuzza, Cristiana, Varvara, Pamela, Ventura, Patrizia, Vicari, Stefano, Vicini, Stefania, von Bentzel, Carolin, Wells, Philip, Williams, Beata, Zabarella, Marina, Zamboni, Anna, Zanetti, Edda, HASH(0x5651c9679ff8), RS: MHeNs - R2 - Mental Health, Psychiatrie & Neuropsychologie, MUMC+: MA Med Staf Spec Psychiatrie (9), Child and Adolescent Psychiatry / Psychology, Epidemiology, Clinical Child and Family Studies, LEARN! - Child rearing, APH - Mental Health, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Lille Neurosciences & Cognition - U 1172 (LilNCog), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre Hospitalier de Versailles André Mignot (CHV), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), CHU Lille, Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, The MILESTONE project was funded by EU FP7 programme under grant number 602442. SPS is part-funded by the National Institute for Health Research (NIHR) Collaboration for Leadership in Applied Health Research and Care West Midlands (NIHR CLAHRC WM), now recommissioned as NIHR Applied Research Collaboration West Midlands. The views expressed in this publication are those of the author(s) and not necessarily those of the NIHR or the Department of Health and Social Care. PS is the co-inventor of the HealthTrackerTM and is the Chief Executive Officer and shareholder in HealthTracker Ltd. FF is a Chief Technical Officer and AK is the Chief Finance Officer employed by HealthTracker Ltd, respectively. FCV publishes the Dutch translations of ASEBA, from which he receives remuneration. AM was a speaker and advisor for Neurim, Shire, Infectopharm, and Lilly (all not related to transition research)., European Project: 602442,EC:FP7:HEALTH,FP7-HEALTH-2013-INNOVATION-1,MILESTONE(2014), The Milestone Consortium, Gerritsen, S, van Bodegom, L, Dieleman, G, Overbeek, M, Verhulst, F, Wolke, D, Rizopoulos, D, Appleton, R, van Amelsvoort, T, Bodier Rethore, C, Bonnet-Brilhault, F, Charvin, I, Da Fonseca, D, Davidovic, N, Dodig-Curkovic, K, Ferrari, A, Fiori, F, Franic, T, Gatherer, C, de Girolamo, G, Heaney, N, Hendrickx, G, Jardri, R, Kolozsvari, A, Lida-Pulik, H, Lievesley, K, Madan, J, Mastroianni, M, Maurice, V, Mcnicholas, F, Nacinovich, R, Parenti, A, Paul, M, Purper-Ouakil, D, Rivolta, L, de Roeck, V, Russet, F, Saam, M, Sagar-Ouriaghli, I, Santosh, P, Sartor, A, Schulze, U, Scocco, P, Signorini, G, Singh, S, Singh, J, Speranza, M, Stagi, P, Stagni, P, Street, C, Tah, P, Tanase, E, Tremmery, S, Tuffrey, A, Tuomainen, H, Walker, L, Wilson, A, Maras, A, Adams, L, Allibrio, G, Armando, M, Aslan, S, Baccanelli, N, Balaudo, M, Bergamo, F, Bertani, A, Berriman, J, Boon, A, Braamse, K, Breuninger, U, Buttiglione, M, Buttle, S, Schandrin, A, Cammarano, M, Canaway, A, Cantini, F, Cappellari, C, Carenini, M, Carra, G, Ferrari, C, Chianura, K, Coleman, P, Colonna, A, Conese, P, Costanzo, R, Daffern, C, Danckaerts, M, de Giacomo, A, Ermans, J, Farmer, A, Fegert, J, Ferrari, S, Galea, G, Gatta, M, Gheza, E, Goglia, G, Grandetto, M, Griffin, J, Levi, F, Humbertclaude, V, Ingravallo, N, Invernizzi, R, Kelly, C, Killilea, M, Kirwan, J, Klockaerts, C, Kovac, V, Liew, A, Lippens, C, Macchi, F, Manenti, L, Margari, F, Margari, L, Martinelli, P, Mcfadden, L, Menghini, D, Miller, S, Monzani, E, Morini, G, Mutafov, T, O'Hara, L, Negrinotti, C, Nelis, E, Neri, F, Nikolova, P, Nossa, M, Cataldo, M, Noterdaeme, M, Operto, F, Panaro, V, Pastore, A, Pemmaraju, V, Pepermans, A, Petruzzelli, M, Presicci, A, Prigent, C, Rinaldi, F, Riva, E, Roekens, A, Rogers, B, Ronzini, P, Sakar, V, Salvetti, S, Martinelli, O, Sandhu, T, Schepker, R, Siviero, M, Slowik, M, Smyth, C, Conti, P, Spadone, M, Starace, F, Stoppa, P, Tansini, L, Toselli, C, Trabucchi, G, Tubito, M, van Dam, A, van Gutschoven, H, van West, D, Vanni, F, Vannicola, C, Varuzza, C, Varvara, P, Ventura, P, Vicari, S, Vicini, S, von Bentzel, C, Wells, P, Williams, B, Zabarella, M, Zamboni, A, and Zanetti, E

Subjects
Adult mental health service, Adult, Mental Health Services, Parents, Health (social science), Child and adolescent mental health service, Social Psychology, RJ, Epidemiology, ADOLESCENT, Child and adolescent mental health services, Adult mental health services, Young adults, Transition, SDG 3 - Good Health and Well-being, PEOPLE, SCHIZOPHRENIA, Humans, Family, Child, Demography, Mental Disorders, CARE, Psychiatry and Mental health, Young adult, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, RA
Abstract

Purpose The service configuration with distinct child and adolescent mental health services (CAMHS) and adult mental health services (AMHS) may be a barrier to continuity of care. Because of a lack of transition policy, CAMHS clinicians have to decide whether and when a young person should transition to AMHS. This study describes which characteristics are associated with the clinicians’ advice to continue treatment at AMHS. Methods Demographic, family, clinical, treatment, and service-use characteristics of the MILESTONE cohort of 763 young people from 39 CAMHS in Europe were assessed using multi-informant and standardized assessment tools. Logistic mixed models were fitted to assess the relationship between these characteristics and clinicians’ transition recommendations. Results Young people with higher clinician-rated severity of psychopathology scores, with self- and parent-reported need for ongoing treatment, with lower everyday functional skills and without self-reported psychotic experiences were more likely to be recommended to continue treatment. Among those who had been recommended to continue treatment, young people who used psychotropic medication, who had been in CAMHS for more than a year, and for whom appropriate AMHS were available were more likely to be recommended to continue treatment at AMHS. Young people whose parents indicated a need for ongoing treatment were more likely to be recommended to stay in CAMHS. Conclusion Although the decision regarding continuity of treatment was mostly determined by a small set of clinical characteristics, the recommendation to continue treatment at AMHS was mostly affected by service-use related characteristics, such as the availability of appropriate services.

Published
2022

7. Cohort profile

Author

Gerritsen, Suzanne E., Maras, Athanasios, van Bodegom, Larissa S., Overbeek, Mathilde M., Verhulst, Frank C., Wolke, Dieter, Appleton, Rebecca, Bertani, Angelo, Cataldo, Maria G., Conti, Patrizia, Da Fonseca, David, Davidović, Nikolina, Dodig-Ćurković, Katarina, Ferrari, Cecilia, Fiori, Federico, Franić, Tomislav, Gatherer, Charlotte, De Girolamo, Giovanni, Heaney, Natalie, Hendrickx, Gaëlle, Kolozsvari, Alfred, Levi, Flavia Micol, Lievesley, Kate, Madan, Jason, Martinelli, Ottaviano, Mastroianni, Mathilde, Maurice, Virginie, McNicholas, Fiona, O'Hara, Lesley, Paul, Moli, Purper-Ouakil, Diane, de Roeck, Veronique, Russet, Frédérick, Saam, Melanie C., Sagar-Ouriaghli, Ilyas, Santosh, Paramala J., Sartor, Anne, Schandrin, Aurélie, Schulze, Ulrike M. E., Signorini, Giulia, Singh, Swaran P., Singh, Jatinder, Street, Cathy, Tah, Priya, Tanase, Elena, Tremmery, Sabine, Tuffrey, Amanda, Tuomainen, Helena, van Amelsvoort, Therese A. M. J., Wilson, Anna, Walker, Leanne, Dieleman, Gwen C., Adams, Laura, Allibrio, Giovanni, Armando, Marco, Aslan, Sonja, Baccanelli, Nadia, Balaudo, Monica, Bergamo, Fabia, Berriman, Jo, Rethore, Chrystèle Bodier, Bonnet-Brilhault, Frédérique, Boon, Albert, Braamse, Karen, Breuninger, Ulrike, Buttiglione, Maura, Buttle, Sarah, Cammarano, Marco, Canaway, Alastair, Cantini, Fortunata, Cappellari, Cristiano, Carenini, Marta, Carrà, Giuseppe, Charvin, Isabelle, Chianura, Krizia, Coleman, Philippa, Colonna, Annalisa, Conese, Patrizia, Costanzo, Raffaella, Daffern, Claire, Danckaerts, Marina, Giacomo, Andrea de, Dineen, Peter, Ermans, Jean-Pierre, Farmer, Alan, Fegert, Jörg M., Ferrari, Alessandro, Ferrari, Sabrina, Galea, Giuliana, Gatta, Michela, Gheza, Elisa, Goglia, Giacomo, Grandetto, MariaRosa, Griffin, James, Healy, Elaine, Holmes, Keith, Humbertclaude, Véronique, Ingravallo, Nicola, Invernizzi, Roberta, Jardri, Renaud, Keeley, Helen, Kelly, Caoimhe, Killilea, Meghan, Kirwan, James, Klockaerts, Catherine, Kovač, Vlatka, Lida-Pulik, Hélène, Liew, Ashley, Lippens, Christel, Lynch, Fionnuala, Macchi, Francesca, Manenti, Lidia, Margari, Francesco, Margari, Lucia, Martinelli, Paola, McDonald, James, McFadden, Leighton, Menghini, Deny, Migone, Maria, Miller, Sarah, Monzani, Emiliano, Morini, Giorgia, Mutafov, Todor, Nacinovich, Renata, Negrinotti, Cristina, Nelis, Emmanuel, Neri, Francesca, Nikolova, Paulina, Nossa, Marzia, Noterdaeme, Michele, Operto, Francesca, Panaro, Vittoria, Parenti, Aesa, Pastore, Adriana, Pemmaraju, Vinuthna, Pepermans, Ann, Petruzzelli, Maria Giuseppina, Presicci, Anna, Prigent, Catherine, Rinaldi, Francesco, Riva, Erika, Rivolta, Laura, Roekens, Anne, Rogers, Ben, Ronzini, Pablo, Sakar, Vehbi, Salvetti, Selena, Sandhu, Tanveer, Schepker, Renate, Scocco, Paolo, Siviero, Marco, Slowik, Michael, Smyth, Courtney, Spadone, Maria Antonietta, Speranza, Mario, Stagi, Paolo, Stagni, Pamela, Starace, Fabrizio, Stoppa, Patrizia, Tansini, Lucia, Toselli, Cecilia, Trabucchi, Guido, Tubito, Maria, Dam, Arno van, Gutschoven, Hanne Van, West, Dirk van, Vanni, Fabio, Vannicola, Chiara, Varuzza, Cristiana, Varvara, Pamela, Ventura, Patrizia, Vicari, Stefano, Vicini, Stefania, Bentzel, Carolin von, Wells, Philip, Williams, Beata, Zabarella, Marina, Zamboni, Anna, Zanetti, Edda, RS: MHeNs - R2 - Mental Health, Psychiatrie & Neuropsychologie, MUMC+: MA Med Staf Spec Psychiatrie (9), Child and Adolescent Psychiatry / Psychology, Clinical Child and Family Studies, LEARN! - Child rearing, and APH - Mental Health

Subjects
Adult, Internationality, SAMPLE, RJ, child & adolescent psychiatry, ADOLESCENT, Jugendpsychiatrie, Cohort Studies, SDG 3 - Good Health and Well-being, ddc:150, QUALITY-OF-LIFE, Psychiatrische Versorgung, Child psychiatry, Humans, Prospective Studies, SCALE, Demography, Retrospective Studies, Psychiatry, Internationalität, OUTCOMES, DDC 150 / Psychology, Adolescent psychiatry, international health services, General Medicine, WHOQOL-BREF, Europe, Mental Health, Mental health services, CROSS, Adolescent Health Services, EXPERIENCE, Kinderpsychiatrie, adult psychiatry, RA, TRANSITION, RC
Abstract

PurposeThe presence of distinct child and adolescent mental health services (CAMHS) and adult mental health services (AMHS) impacts continuity of mental health treatment for young people. However, we do not know the extent of discontinuity of care in Europe nor the effects of discontinuity on the mental health of young people. Current research is limited, as the majority of existing studies are retrospective, based on small samples or used non-standardised information from medical records. The MILESTONE prospective cohort study aims to examine associations between service use, mental health and other outcomes over 24 months, using information from self, parent and clinician reports.ParticipantsSeven hundred sixty-three young people from 39 CAMHS in 8 European countries, their parents and CAMHS clinicians who completed interviews and online questionnaires and were followed up for 2 years after reaching the upper age limit of the CAMHS they receive treatment at.Findings to dateThis cohort profile describes the baseline characteristics of the MILESTONE cohort. The mental health of young people reaching the upper age limit of their CAMHS varied greatly in type and severity: 32.8% of young people reported clinical levels of self-reported problems and 18.6% were rated to be ‘markedly ill’, ‘severely ill’ or ‘among the most extremely ill’ by their clinician. Fifty-seven per cent of young people reported psychotropic medication use in the previous half year.Future plansAnalysis of longitudinal data from the MILESTONE cohort will be used to assess relationships between the demographic and clinical characteristics of young people reaching the upper age limit of their CAMHS and the type of care the young person uses over the next 2 years, such as whether the young person transitions to AMHS. At 2 years follow-up, the mental health outcomes of young people following different care pathways will be compared.Trial registration numberNCT03013595., publishedVersion

Published
2021

9. Helicobacter pylori infection has a detrimental impact on the efficacy of cancer immunotherapies

Author

Smith, James, Vaillant, Laurie, Oster, Paul, Riva, Erika, McMillan, Brynn, Begka, Christina, and Truntzer, Caroline

Abstract

Objective: In this study, we determined whether Helicobacter pylori (H. pylori) infection dampens the efficacy of cancer immunotherapies. Design: Using mouse models, we evaluated whether immune checkpoint inhibitors or vaccine-based immunotherapies are effective in reducing tumour volumes of H. pylori-infected mice. In humans, we evaluated the correlation between H. pylori seropositivity and the efficacy of the programmed cell death protein 1 (PD-1) blockade therapy in patients with non-small-cell lung cancer (NSCLC). Results: In mice engrafted with MC38 colon adenocarcinoma or B16-OVA melanoma cells, the tumour volumes of non-infected mice undergoing anticytotoxic T-lymphocyte-associated protein 4 and/or programmed death ligand 1 or anti-cancer vaccine treatments were significantly smaller than those of infected mice. We observed a decreased number and activation status of tumour-specific CD8+ T cells in the tumours of infected mice treated with cancer immunotherapies independent of the gut microbiome composition. Additionally, by performing an in vitro co-culture assay, we observed that dendritic cells of infected mice promote lower tumour-specific CD8+ T cell proliferation. We performed retrospective human clinical studies in two independent cohorts. In the Dijon cohort, H. pylori seropositivity was found to be associated with a decreased NSCLC patient survival on anti-PD-1 therapy. The survival median for H. pylori seropositive patients was 6.7 months compared with 15.4 months for seronegative patients (p=0.001). Additionally, in the Montreal cohort, H. pylori seropositivity was found to be associated with an apparent decrease of NSCLC patient progression-free survival on anti-PD-1 therapy. Conclusion: Our study unveils for the first time that the stomach microbiota affects the response to cancer immunotherapies and that H. pylori serology would be a powerful tool to personalize cancer immunotherapy treatment. https://www.pittsburghtribune.org/ https://amazonsale.io/ https://ehealthcareplus.us/ https://www.timessquarereporter.com/ https://edu.pittsburghtribune.org/ https://www.infinityebook.com/ https://www.1stsupplement.com/ https://batik4d.vip/ https://eurl.live/https://eurl.live/us/ https://ingredients.ning.com/ https://jeffbezos.ning.com/

Published
2022
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11. Helicobacter pylori infection has a detrimental impact on the efficacy of cancer immunotherapies

Author

Oster, Paul, primary, Vaillant, Laurie, additional, Riva, Erika, additional, McMillan, Brynn, additional, Begka, Christina, additional, Truntzer, Caroline, additional, Richard, Corentin, additional, Leblond, Marine M, additional, Messaoudene, Meriem, additional, Machremi, Elisavet, additional, Limagne, Emeric, additional, Ghiringhelli, Francois, additional, Routy, Bertrand, additional, Verdeil, Gregory, additional, and Velin, Dominique, additional

Published
2021
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13. Helicobacter pylori infection has a detrimental impact on the efficacy of cancer immunotherapies.

Author

Oster, Paul, Vaillant, Laurie, Riva, Erika, McMillan, Brynn, Begka, Christina, Truntzer, Caroline, Richard, Corentin, Leblond, Marine M, Messaoudene, Meriem, Machremi, Elisavet, Limagne, Emeric, Ghiringhelli, Francois, Routy, Bertrand, Verdeil, Gregory, and Velin, Dominique

Subjects
HELICOBACTER pylori infections, BACTEROIDES fragilis, DERMATOPHAGOIDES pteronyssinus, BACTERIAL colonies, TUMOR-infiltrating immune cells
Published
2022
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15. Helicobacter pyloriinfection has a detrimental impact on the efficacy of cancer immunotherapies

Author

Oster, Paul, Vaillant, Laurie, Riva, Erika, McMillan, Brynn, Begka, Christina, Truntzer, Caroline, Richard, Corentin, Leblond, Marine M, Messaoudene, Meriem, Machremi, Elisavet, Limagne, Emeric, Ghiringhelli, Francois, Routy, Bertrand, Verdeil, Gregory, and Velin, Dominique

Abstract

ObjectiveIn this study, we determined whether Helicobacter pylori(H. pylori) infection dampens the efficacy of cancer immunotherapies.DesignUsing mouse models, we evaluated whether immune checkpoint inhibitors or vaccine-based immunotherapies are effective in reducing tumour volumes of H. pylori-infected mice. In humans, we evaluated the correlation between H. pyloriseropositivity and the efficacy of the programmed cell death protein 1 (PD-1) blockade therapy in patients with non-small-cell lung cancer (NSCLC).ResultsIn mice engrafted with MC38 colon adenocarcinoma or B16-OVA melanoma cells, the tumour volumes of non-infected mice undergoing anticytotoxic T-lymphocyte-associated protein 4 and/or programmed death ligand 1 or anti-cancer vaccine treatments were significantly smaller than those of infected mice. We observed a decreased number and activation status of tumour-specific CD8+T cells in the tumours of infected mice treated with cancer immunotherapies independent of the gut microbiome composition. Additionally, by performing an in vitro co-culture assay, we observed that dendritic cells of infected mice promote lower tumour-specific CD8+T cell proliferation. We performed retrospective human clinical studies in two independent cohorts. In the Dijon cohort, H. pyloriseropositivity was found to be associated with a decreased NSCLC patient survival on anti-PD-1 therapy. The survival median for H. pyloriseropositive patients was 6.7 months compared with 15.4 months for seronegative patients (p=0.001). Additionally, in the Montreal cohort, H. pyloriseropositivity was found to be associated with an apparent decrease of NSCLC patient progression-free survival on anti-PD-1 therapy.ConclusionOur study unveils for the first time that the stomach microbiota affects the response to cancer immunotherapies and that H. pyloriserology would be a powerful tool to personalize cancer immunotherapy treatment.

Published
2022
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17. Abstract A11: Development and beta testing of a culturally appropriate research literacy support tool to increase research participation among minority and underrepresented populations

Author

Riva, Erika E. de la, primary, Haring, Rodney, additional, Rodriguez, Elisa M., additional, Gonzalez, Evelyn, additional, Katz, Mira, additional, Clark, Nikia, additional, Henry, Whitney Ann E., additional, Ortiz, Rosa O., additional, Zimmermann, Barret J., additional, Clayman, Marla L., additional, Erwin, Deborah O., additional, Kaur, Judith S., additional, and Simon, Melissa A., additional

Published
2017
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24. Dietary Fiber Confers Protection against Flu by Shaping Ly6c - Patrolling Monocyte Hematopoiesis and CD8 + T Cell Metabolism.

Author

Trompette A, Gollwitzer ES, Pattaroni C, Lopez-Mejia IC, Riva E, Pernot J, Ubags N, Fajas L, Nicod LP, and Marsland BJ

Subjects
Adaptive Immunity drug effects, Adaptive Immunity immunology, Animals, CD8-Positive T-Lymphocytes metabolism, Dietary Fiber administration & dosage, Fatty Acids, Volatile immunology, Fatty Acids, Volatile metabolism, Hematopoiesis drug effects, Humans, Immunity, Innate drug effects, Immunity, Innate immunology, Mice, Inbred BALB C, Mice, Inbred C57BL, Mice, Knockout, Monocytes drug effects, Monocytes metabolism, Protective Agents administration & dosage, Protective Agents pharmacology, Antigens, Ly immunology, CD8-Positive T-Lymphocytes immunology, Dietary Fiber pharmacology, Hematopoiesis immunology, Monocytes immunology, Orthomyxoviridae Infections immunology
Abstract

Dietary fiber protects against chronic inflammatory diseases by dampening immune responses through short-chain fatty acids (SCFAs). Here we examined the effect of dietary fiber in viral infection, where the anti-inflammatory properties of SCFAs in principle could prevent protective immunity. Instead, we found that fermentable dietary fiber increased survival of influenza-infected mice through two complementary mechanisms. High-fiber diet (HFD)-fed mice exhibited altered bone marrow hematopoiesis, characterized by enhanced generation of Ly6c - patrolling monocytes, which led to increased numbers of alternatively activated macrophages with a limited capacity to produce the chemokine CXCL1 in the airways. Blunted CXCL1 production reduced neutrophil recruitment to the airways, thus limiting tissue immunopathology during infection. In parallel, diet-derived SCFAs boosted CD8 + T cell effector function by enhancing cellular metabolism. Hence, dietary fermentable fiber and SCFAs set an immune equilibrium, balancing innate and adaptive immunity so as to promote the resolution of influenza infection while preventing immune-associated pathology., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Published
2018
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