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1. Orthogonal cytokine engineering enables novel synthetic effector states escaping canonical exhaustion in tumor-rejecting CD8+ T cells

Author

Corria-Osorio, Jesus, Carmona, Santiago J., Stefanidis, Evangelos, Andreatta, Massimo, Ortiz-Miranda, Yaquelin, Muller, Tania, Rota, Ioanna A., Crespo, Isaac, Seijo, Bili, Castro, Wilson, Jimenez-Luna, Cristina, Scarpellino, Leonardo, Ronet, Catherine, Spill, Aodrenn, Lanitis, Evripidis, Romero, Pedro, Luther, Sanjiv A., Irving, Melita, and Coukos, George

Published
2023
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2. Supplementary Figure Legends from Trifluridine/Tipiracil plus Oxaliplatin Improves PD-1 Blockade in Colorectal Cancer by Inducing Immunogenic Cell Death and Depleting Macrophages

Author

Limagne, Emeric, primary, Thibaudin, Marion, primary, Nuttin, Lisa, primary, Spill, Aodrenn, primary, Derangère, Valentin, primary, Fumet, Jean-David, primary, Amellal, Nadia, primary, Peranzoni, Elisa, primary, Cattan, Valérie, primary, and Ghiringhelli, François, primary

Published
2023
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4. Supplementary Table 2 from Trifluridine/Tipiracil plus Oxaliplatin Improves PD-1 Blockade in Colorectal Cancer by Inducing Immunogenic Cell Death and Depleting Macrophages

Author

Limagne, Emeric, primary, Thibaudin, Marion, primary, Nuttin, Lisa, primary, Spill, Aodrenn, primary, Derangère, Valentin, primary, Fumet, Jean-David, primary, Amellal, Nadia, primary, Peranzoni, Elisa, primary, Cattan, Valérie, primary, and Ghiringhelli, François, primary

Published
2023
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5. Supplementary Table 1 from Trifluridine/Tipiracil plus Oxaliplatin Improves PD-1 Blockade in Colorectal Cancer by Inducing Immunogenic Cell Death and Depleting Macrophages

Author

Limagne, Emeric, primary, Thibaudin, Marion, primary, Nuttin, Lisa, primary, Spill, Aodrenn, primary, Derangère, Valentin, primary, Fumet, Jean-David, primary, Amellal, Nadia, primary, Peranzoni, Elisa, primary, Cattan, Valérie, primary, and Ghiringhelli, François, primary

Published
2023
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7. Supplementary Table from Low-Dose Radiotherapy Reverses Tumor Immune Desertification and Resistance to Immunotherapy

Author

Herrera, Fernanda G., primary, Ronet, Catherine, primary, Ochoa de Olza, Maria, primary, Barras, David, primary, Crespo, Isaac, primary, Andreatta, Massimo, primary, Corria-Osorio, Jesus, primary, Spill, Aodrenn, primary, Benedetti, Fabrizio, primary, Genolet, Raphael, primary, Orcurto, Angela, primary, Imbimbo, Martina, primary, Ghisoni, Eleonora, primary, Navarro Rodrigo, Blanca, primary, Berthold, Dominik R., primary, Sarivalasis, Apostolos, primary, Zaman, Khalil, primary, Duran, Rafael, primary, Dromain, Clarisse, primary, Prior, John, primary, Schaefer, Niklaus, primary, Bourhis, Jean, primary, Dimopoulou, Georgia, primary, Tsourti, Zoi, primary, Messemaker, Marius, primary, Smith, Thomas, primary, Warren, Sarah E., primary, Foukas, Periklis, primary, Rusakiewicz, Sylvie, primary, Pittet, Mikaël J., primary, Zimmermann, Stefan, primary, Sempoux, Christine, primary, Dafni, Urania, primary, Harari, Alexandre, primary, Kandalaft, Lana E., primary, Carmona, Santiago J., primary, Dangaj Laniti, Denarda, primary, Irving, Melita, primary, and Coukos, George, primary

Published
2023
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8. Supplementary Figure from Low-Dose Radiotherapy Reverses Tumor Immune Desertification and Resistance to Immunotherapy

Author

Herrera, Fernanda G., primary, Ronet, Catherine, primary, Ochoa de Olza, Maria, primary, Barras, David, primary, Crespo, Isaac, primary, Andreatta, Massimo, primary, Corria-Osorio, Jesus, primary, Spill, Aodrenn, primary, Benedetti, Fabrizio, primary, Genolet, Raphael, primary, Orcurto, Angela, primary, Imbimbo, Martina, primary, Ghisoni, Eleonora, primary, Navarro Rodrigo, Blanca, primary, Berthold, Dominik R., primary, Sarivalasis, Apostolos, primary, Zaman, Khalil, primary, Duran, Rafael, primary, Dromain, Clarisse, primary, Prior, John, primary, Schaefer, Niklaus, primary, Bourhis, Jean, primary, Dimopoulou, Georgia, primary, Tsourti, Zoi, primary, Messemaker, Marius, primary, Smith, Thomas, primary, Warren, Sarah E., primary, Foukas, Periklis, primary, Rusakiewicz, Sylvie, primary, Pittet, Mikaël J., primary, Zimmermann, Stefan, primary, Sempoux, Christine, primary, Dafni, Urania, primary, Harari, Alexandre, primary, Kandalaft, Lana E., primary, Carmona, Santiago J., primary, Dangaj Laniti, Denarda, primary, Irving, Melita, primary, and Coukos, George, primary

Published
2023
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9. Supplementary Data from Low-Dose Radiotherapy Reverses Tumor Immune Desertification and Resistance to Immunotherapy

Author

Herrera, Fernanda G., primary, Ronet, Catherine, primary, Ochoa de Olza, Maria, primary, Barras, David, primary, Crespo, Isaac, primary, Andreatta, Massimo, primary, Corria-Osorio, Jesus, primary, Spill, Aodrenn, primary, Benedetti, Fabrizio, primary, Genolet, Raphael, primary, Orcurto, Angela, primary, Imbimbo, Martina, primary, Ghisoni, Eleonora, primary, Navarro Rodrigo, Blanca, primary, Berthold, Dominik R., primary, Sarivalasis, Apostolos, primary, Zaman, Khalil, primary, Duran, Rafael, primary, Dromain, Clarisse, primary, Prior, John, primary, Schaefer, Niklaus, primary, Bourhis, Jean, primary, Dimopoulou, Georgia, primary, Tsourti, Zoi, primary, Messemaker, Marius, primary, Smith, Thomas, primary, Warren, Sarah E., primary, Foukas, Periklis, primary, Rusakiewicz, Sylvie, primary, Pittet, Mikaël J., primary, Zimmermann, Stefan, primary, Sempoux, Christine, primary, Dafni, Urania, primary, Harari, Alexandre, primary, Kandalaft, Lana E., primary, Carmona, Santiago J., primary, Dangaj Laniti, Denarda, primary, Irving, Melita, primary, and Coukos, George, primary

Published
2023
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10. Data from Low-Dose Radiotherapy Reverses Tumor Immune Desertification and Resistance to Immunotherapy

Author

Herrera, Fernanda G., primary, Ronet, Catherine, primary, Ochoa de Olza, Maria, primary, Barras, David, primary, Crespo, Isaac, primary, Andreatta, Massimo, primary, Corria-Osorio, Jesus, primary, Spill, Aodrenn, primary, Benedetti, Fabrizio, primary, Genolet, Raphael, primary, Orcurto, Angela, primary, Imbimbo, Martina, primary, Ghisoni, Eleonora, primary, Navarro Rodrigo, Blanca, primary, Berthold, Dominik R., primary, Sarivalasis, Apostolos, primary, Zaman, Khalil, primary, Duran, Rafael, primary, Dromain, Clarisse, primary, Prior, John, primary, Schaefer, Niklaus, primary, Bourhis, Jean, primary, Dimopoulou, Georgia, primary, Tsourti, Zoi, primary, Messemaker, Marius, primary, Smith, Thomas, primary, Warren, Sarah E., primary, Foukas, Periklis, primary, Rusakiewicz, Sylvie, primary, Pittet, Mikaël J., primary, Zimmermann, Stefan, primary, Sempoux, Christine, primary, Dafni, Urania, primary, Harari, Alexandre, primary, Kandalaft, Lana E., primary, Carmona, Santiago J., primary, Dangaj Laniti, Denarda, primary, Irving, Melita, primary, and Coukos, George, primary

Published
2023
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11. Abstract 1296: MEK inhibition overcomes chemoimmunotherapy resistance by inducing CXCL10 in cancer cells

Author

Limagne, Emeric, primary, Nuttin, Lisa, additional, Thibaudin, Marion, additional, Jacquin, Elise, additional, Aucagne, Romain, additional, Bon, Marjorie, additional, Ballot, Elise, additional, Revy, Solène, additional, Barnestein, Robby, additional, Truntzer, Caroline, additional, Derangère, Valentin, additional, Fumet, Jean-David, additional, Cédric, Rébé, additional, Bellaye, Pierre-Simon, additional, Kaderbhai, Coureche-Guillaume, additional, Spill, Aodrenn, additional, Collin, Bertrand, additional, Callanan, Mary, additional, Lagrange, Aurélie, additional, Favier, Laure, additional, Coudert, Bruno, additional, Arnould, Laurent, additional, Ladoire, Sylvain, additional, Routy, Bertrand, additional, Joubert, Philippe, additional, and Ghiringhelli, François, additional

Published
2022
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12. Orthogonal Gene Engineering Enables CD8+ T Cells to Control Tumors through a Novel PD-1+TOX-indifferent Synthetic Effector State

Author

Corria-Osorio, Jesus, primary, Carmona, Santiago J., additional, Stefanidis, Evangelos, additional, Andreatta, Massimo, additional, Muller, Tania, additional, Ortiz-Miranda, Yaquelin, additional, Seijo, Bili, additional, Castro, Wilson, additional, Jimenez-Luna, Cristina, additional, Scarpellino, Leonardo, additional, Ronet, Catherine, additional, Spill, Aodrenn, additional, Lanitis, Evripidis, additional, Luther, Sanjiv A., additional, Romero, Pedro, additional, Irving, Melita, additional, and Coukos, George, additional

Published
2022
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13. MEK inhibition overcomes chemoimmunotherapy resistance by inducing CXCL10 in cancer cells

Author

Limagne, Emeric, primary, Nuttin, Lisa, additional, Thibaudin, Marion, additional, Jacquin, Elise, additional, Aucagne, Romain, additional, Bon, Marjorie, additional, Revy, Solène, additional, Barnestein, Robby, additional, Ballot, Elise, additional, Truntzer, Caroline, additional, Derangère, Valentin, additional, Fumet, Jean-David, additional, Latour, Charlène, additional, Rébé, Cédric, additional, Bellaye, Pierre-Simon, additional, Kaderbhaï, Coureche-Guillaume, additional, Spill, Aodrenn, additional, Collin, Bertrand, additional, Callanan, Mary B., additional, Lagrange, Aurélie, additional, Favier, Laure, additional, Coudert, Bruno, additional, Arnould, Laurent, additional, Ladoire, Sylvain, additional, Routy, Bertrand, additional, Joubert, Philippe, additional, and Ghiringhelli, François, additional

Published
2022
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14. Low-Dose Radiotherapy Reverses Tumor Immune Desertification and Resistance to Immunotherapy

Author

Herrera, Fernanda G., primary, Ronet, Catherine, additional, Ochoa de Olza, Maria, additional, Barras, David, additional, Crespo, Isaac, additional, Andreatta, Massimo, additional, Corria-Osorio, Jesus, additional, Spill, Aodrenn, additional, Benedetti, Fabrizio, additional, Genolet, Raphael, additional, Orcurto, Angela, additional, Imbimbo, Martina, additional, Ghisoni, Eleonora, additional, Navarro Rodrigo, Blanca, additional, Berthold, Dominik R., additional, Sarivalasis, Apostolos, additional, Zaman, Khalil, additional, Duran, Rafael, additional, Dromain, Clarisse, additional, Prior, John, additional, Schaefer, Niklaus, additional, Bourhis, Jean, additional, Dimopoulou, Georgia, additional, Tsourti, Zoi, additional, Messemaker, Marius, additional, Smith, Thomas, additional, Warren, Sarah E., additional, Foukas, Periklis, additional, Rusakiewicz, Sylvie, additional, Pittet, Mikaël J., additional, Zimmermann, Stefan, additional, Sempoux, Christine, additional, Dafni, Urania, additional, Harari, Alexandre, additional, Kandalaft, Lana E., additional, Carmona, Santiago J., additional, Dangaj Laniti, Denarda, additional, Irving, Melita, additional, and Coukos, George, additional

Published
2021
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16. Orthogonal cytokine engineering enables novel synthetic effector states escaping canonical exhaustion in tumor-rejecting CD8+T cells

Author

Corria-Osorio, Jesus, Carmona, Santiago J., Stefanidis, Evangelos, Andreatta, Massimo, Ortiz-Miranda, Yaquelin, Muller, Tania, Rota, Ioanna A., Crespo, Isaac, Seijo, Bili, Castro, Wilson, Jimenez-Luna, Cristina, Scarpellino, Leonardo, Ronet, Catherine, Spill, Aodrenn, Lanitis, Evripidis, Romero, Pedro, Luther, Sanjiv A., Irving, Melita, and Coukos, George

Abstract

To date, no immunotherapy approaches have managed to fully overcome T-cell exhaustion, which remains a mandatory fate for chronically activated effector cells and a major therapeutic challenge. Understanding how to reprogram CD8+tumor-infiltrating lymphocytes away from exhausted effector states remains an elusive goal. Our work provides evidence that orthogonal gene engineering of T cells to secrete an interleukin (IL)-2 variant binding the IL-2Rβγ receptor and the alarmin IL-33 reprogrammed adoptively transferred T cells to acquire a novel, synthetic effector state, which deviated from canonical exhaustion and displayed superior effector functions. These cells successfully overcame homeostatic barriers in the host and led—in the absence of lymphodepletion or exogenous cytokine support—to high levels of engraftment and tumor regression. Our work unlocks a new opportunity of rationally engineering synthetic CD8+T-cell states endowed with the ability to avoid exhaustion and control advanced solid tumors.

Published
2023
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18. Trifluridine/Tipiracil plus Oxaliplatin Improves PD-1 Blockade in Colorectal Cancer by Inducing Immunogenic Cell Death and Depleting Macrophages

Author

Limagne, Emeric, primary, Thibaudin, Marion, additional, Nuttin, Lisa, additional, Spill, Aodrenn, additional, Derangère, Valentin, additional, Fumet, Jean-David, additional, Amellal, Nadia, additional, Peranzoni, Elisa, additional, Cattan, Valérie, additional, and Ghiringhelli, François, additional

Published
2019
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21. Optimized gene engineering of murine CAR-T cells reveals the beneficial effects of IL-15 coexpression

Author

Lanitis, Evripidis, Rota, Giorgia, Kosti, Paris, Ronet, Catherine, Spill, Aodrenn, Seijo, Bili, Romero, Pedro, Dangaj, Denarda, Coukos, George, and Irving, Melita

Abstract

Limited clinical benefit has been demonstrated for chimeric antigen receptor (CAR) therapy of solid tumors, but coengineering strategies to generate so-called fourth-generation (4G) CAR-T cells are advancing toward overcoming barriers in the tumor microenvironment (TME) for improved responses. In large part due to technical challenges, there are relatively few preclinical CAR therapy studies in immunocompetent, syngeneic tumor-bearing mice. Here, we describe optimized methods for the efficient retroviral transduction and expansion of murine T lymphocytes of a predominantly central memory T cell (TCM cell) phenotype. We present a bicistronic retroviral vector encoding both a tumor vasculature–targeted CAR and murine interleukin-15 (mIL-15), conferring enhanced effector functions, engraftment, tumor control, and TME reprogramming, including NK cell activation and reduced presence of M2 macrophages. The 4G-CAR-T cells coexpressing mIL-15 were further characterized by up-regulation of the antiapoptotic marker Bcl-2 and lower cell-surface expression of the inhibitory receptor PD-1. Overall, this work introduces robust tools for the development and evaluation of 4G-CAR-T cells in immunocompetent mice, an important step toward the acceleration of effective therapies reaching the clinic.

Published
2021
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22. Low-Dose Radiotherapy Reverses Tumor Immune Desertification and Resistance to Immunotherapy.

Author

Herrera FG, Ronet C, Ochoa de Olza M, Barras D, Crespo I, Andreatta M, Corria-Osorio J, Spill A, Benedetti F, Genolet R, Orcurto A, Imbimbo M, Ghisoni E, Navarro Rodrigo B, Berthold DR, Sarivalasis A, Zaman K, Duran R, Dromain C, Prior J, Schaefer N, Bourhis J, Dimopoulou G, Tsourti Z, Messemaker M, Smith T, Warren SE, Foukas P, Rusakiewicz S, Pittet MJ, Zimmermann S, Sempoux C, Dafni U, Harari A, Kandalaft LE, Carmona SJ, Dangaj Laniti D, Irving M, and Coukos G

Subjects
Adaptive Immunity, Adenocarcinoma, Papillary immunology, Animals, CD4-Positive T-Lymphocytes, CD8-Positive T-Lymphocytes, Disease Models, Animal, Female, Humans, Lymphocytes, Tumor-Infiltrating, Mice, Mice, Inbred C57BL, Ovarian Neoplasms immunology, Radiotherapy Dosage, Tumor Microenvironment, Adenocarcinoma, Papillary radiotherapy, Ovarian Neoplasms radiotherapy
Abstract

Developing strategies to inflame tumors is critical for increasing response to immunotherapy. Here, we report that low-dose radiotherapy (LDRT) of murine tumors promotes T-cell infiltration and enables responsiveness to combinatorial immunotherapy in an IFN-dependent manner. Treatment efficacy relied upon mobilizing both adaptive and innate immunity and depended on both cytotoxic CD4 + and CD8 + T cells. LDRT elicited predominantly CD4 + cells with features of exhausted effector cytotoxic cells, with a subset expressing NKG2D and exhibiting proliferative capacity, as well as a unique subset of activated dendritic cells expressing the NKG2D ligand RAE1. We translated these findings to a phase I clinical trial administering LDRT, low-dose cyclophosphamide, and immune checkpoint blockade to patients with immune-desert tumors. In responsive patients, the combinatorial treatment triggered T-cell infiltration, predominantly of CD4 + cells with Th1 signatures. Our data support the rational combination of LDRT with immunotherapy for effectively treating low T cell-infiltrated tumors. SIGNIFICANCE: Low-dose radiation reprogrammed the tumor microenvironment of tumors with scarce immune infiltration and together with immunotherapy induced simultaneous mobilization of innate and adaptive immunity, predominantly CD4 + effector T cells, to achieve tumor control dependent on NKG2D. The combination induced important responses in patients with metastatic immune-cold tumors. This article is highlighted in the In This Issue feature, p. 1 ., (©2021 The Authors; Published by the American Association for Cancer Research.)

Published
2022
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