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2. Successful Anti-PD-1 Cancer Immunotherapy Requires T Cell-Dendritic Cell Crosstalk Involving the Cytokines IFN-γ and IL-12.

Author

Garris, Christopher S, Arlauckas, Sean P, Kohler, Rainer H, Trefny, Marcel P, Garren, Seth, Piot, Cécile, Engblom, Camilla, Pfirschke, Christina, Siwicki, Marie, Gungabeesoon, Jeremy, Freeman, Gordon J, Warren, Sarah E, Ong, SuFey, Browning, Erica, Twitty, Christopher G, Pierce, Robert H, Le, Mai H, Algazi, Alain P, Daud, Adil I, Pai, Sara I, Zippelius, Alfred, Weissleder, Ralph, and Pittet, Mikael J

Subjects
Dendritic Cells, T-Lymphocytes, Animals, Mice, Inbred C57BL, Mice, Transgenic, Humans, Neoplasms, NF-kappa B, Interleukin-12, Antibodies, Monoclonal, Immunotherapy, Signal Transduction, Adult, Aged, Aged, 80 and over, Middle Aged, Female, Male, Interferon-gamma, Programmed Cell Death 1 Receptor, IFN-γ, IL-12, anti-PD-1, cancer, checkpoint, dendritic cell, immunotherapy, non-canonical NF-κB, Vaccine Related, Cancer, Immunization, Aetiology, 2.1 Biological and endogenous factors, Inflammatory and immune system, Immunology
Abstract

Anti-PD-1 immune checkpoint blockers can induce sustained clinical responses in cancer but how they function in vivo remains incompletely understood. Here, we combined intravital real-time imaging with single-cell RNA sequencing analysis and mouse models to uncover anti-PD-1 pharmacodynamics directly within tumors. We showed that effective antitumor responses required a subset of tumor-infiltrating dendritic cells (DCs), which produced interleukin 12 (IL-12). These DCs did not bind anti-PD-1 but produced IL-12 upon sensing interferon γ (IFN-γ) that was released from neighboring T cells. In turn, DC-derived IL-12 stimulated antitumor T cell immunity. These findings suggest that full-fledged activation of antitumor T cells by anti-PD-1 is not direct, but rather involves T cell:DC crosstalk and is licensed by IFN-γ and IL-12. Furthermore, we found that activating the non-canonical NF-κB transcription factor pathway amplified IL-12-producing DCs and sensitized tumors to anti-PD-1 treatment, suggesting a therapeutic strategy to improve responses to checkpoint blockade.

Published
2018

3. DUX4 expression activates JNK and p38 MAP kinases in myoblasts

Author

Brennan, Christopher M., primary, Hill, Abby S., additional, St. Andre, Michael, additional, Li, Xianfeng, additional, Madeti, Vijaya, additional, Breitkopf, Susanne, additional, Garren, Seth, additional, Xue, Liang, additional, Gilbert, Tamara, additional, Hadjipanayis, Angela, additional, Monetti, Mara, additional, Emerson, Charles P., additional, Moccia, Robert, additional, Owens, Jane, additional, and Christoforou, Nicolas, additional

Published
2022
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4. Successful Anti-PD-1 Cancer Immunotherapy Requires T Cell-Dendritic Cell Crosstalk Involving the Cytokines IFN-γ and IL-12

Author

Garris, Christopher S., primary, Arlauckas, Sean P., additional, Kohler, Rainer H., additional, Trefny, Marcel P., additional, Garren, Seth, additional, Piot, Cécile, additional, Engblom, Camilla, additional, Pfirschke, Christina, additional, Siwicki, Marie, additional, Gungabeesoon, Jeremy, additional, Freeman, Gordon J., additional, Warren, Sarah E., additional, Ong, SuFey, additional, Browning, Erica, additional, Twitty, Christopher G., additional, Pierce, Robert H., additional, Le, Mai H., additional, Algazi, Alain P., additional, Daud, Adil I., additional, Pai, Sara I., additional, Zippelius, Alfred, additional, Weissleder, Ralph, additional, and Pittet, Mikael J., additional

Published
2022
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5. CRISPR-mediated correction of skeletal muscle Ca2+handling in a novel DMD patient-derived pluripotent stem cell model

Author

Morera, Cristina, primary, Kim, Jihee, additional, Paredes-Redondo, Amaia, additional, Nobles, Muriel, additional, Rybin, Denis, additional, Moccia, Robert, additional, Kowala, Anna, additional, Meng, Jinhong, additional, Garren, Seth, additional, Liu, Pentao, additional, Morgan, Jennifer E, additional, Muntoni, Francesco, additional, Christoforou, Nicolas, additional, Owens, Jane, additional, Tinker, Andrew, additional, and Lin, Yung-Yao, additional

Published
2022
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