By analyzing T cells from pre- and post- anti-PD-1 treatment matched tissue biopsies from three independent cohorts of patients with cancer, Wang and Zha et al. showed that higher proportions of CD200+ TILs associated positively with patients’ clinical outcomes. In multiple mouse tumor models, anti-PD-L1 response required CD200+CD8+PD-1+ TILs, which were enriched for tumor antigen-specificity and CTL transcriptional pathways and effector functions. Growth of transplanted tumor cells in mice was controlled more effectively by CD200+ than CD200- CD3+CD8+PD-1+ TIL co-injection. Higher CD200+ CTL infiltration was associated with ICB efficacy in six patient cohorts.
Contributed by Paula Hochman
ABSTRACT: Anti-PD-1/PD-L1 therapy, either by anti-PD-1 antibody or anti-PD-L1 antibody, has efficacy by reinvigorating tumor-infiltrating CD8(+) T cells in a subset of patients with cancer, but it has unequal effects on heterogeneous CD8(+) T cell populations. Hence, the subset crucial to efficacious PD-1 blockade therapy remains elusive. Here, we found an increase in tumor-infiltrating CD200(+) cytotoxic T lymphocytes (CTLs) upon PD-1/PD-L1 blockade, with higher proportions of CD200(+) T cells positively related to a favorable clinical outcome to anti-PD-1/PD-L1 therapy in three independent cohorts of patients with cancer. Using multiple mouse tumor models, we demonstrated that CD200(+) CTLs are essential for efficacious anti-PD-L1 therapy. Mechanistically, we observed a unique chromatin landscape in CD200(+) CTLs and found that these cells are enriched for tumor antigen-specific CTLs and have antitumor effector functions. Coinoculation of CD200(+) CTLs with tumor cells led to robust tumor regression in two transplanted mouse models. Clinically, we found that infiltration of CD200(+) CTLs into tumors could predict immunotherapy efficacy in six patient cohorts. Together, our findings reveal that CD200(+) CTLs in the tumor microenvironment are crucial for efficacious anti-PD-1/PD-L1 therapy and could serve as a predictor of successful immunotherapy in the clinic.
Author Info: (1) Institute of Cancer, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, P. R. China. (2) Institute of Cancer, Xinqiao Hospital, Third Military Medical Unive
Author Info: (1) Institute of Cancer, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, P. R. China. (2) Institute of Cancer, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, P. R. China. Department of Oncology, PLA Rocket Force Characteristic Medical Center, Beijing 100088, P. R. China. (3) Cardiothoracic Surgery Department, Southwest Hospital, Third Military Medical University, Chongqing 400037, P. R. China. (4) Institute of Cancer, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, P. R. China. (5) Institute of Cancer, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, P. R. China. (6) Research Institute, GloriousMed Clinical Laboratory (Shanghai) Co. Ltd., 201318, P. R. China. (7) Institute of Cancer, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, P. R. China. (8) Institute of Cancer, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, P. R. China. (9) Institute of Cancer, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, P. R. China. (10) Institute of Cancer, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, P. R. China. (11) Institute of Cancer, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, P. R. China. (12) Department of Oncology, PLA Rocket Force Characteristic Medical Center, Beijing 100088, P. R. China. (13) Institute of Cancer, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, P. R. China. (14) Institute of Cancer, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, P. R. China. (15) Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA. (16) Department of Immunology, Duke University Medical Center, Durham, NC 27710, USA. (17) Blizard Institute, Barts and London School of Medicine and Dentistry, University of London, London, E1 2AT UK. (18) Institute of Cancer, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, P. R. China. (19) Institute of Cancer, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, P. R. China.
