| First Author | Garris CS | Year | 2018 |
| Journal | Immunity | Volume | 49 |
| Issue | 6 | Pages | 1148-1161.e7 |
| PubMed ID | 30552023 | Mgi Jnum | J:285378 |
| Mgi Id | MGI:6389891 | Doi | 10.1016/j.immuni.2018.09.024 |
| Citation | Garris CS, et al. (2018) Successful Anti-PD-1 Cancer Immunotherapy Requires T Cell-Dendritic Cell Crosstalk Involving the Cytokines IFN-gamma and IL-12. Immunity 49(6):1148-1161.e7 |
| abstractText | 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 gamma (IFN-gamma) 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-gamma and IL-12. Furthermore, we found that activating the non-canonical NF-kappaB 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. |
