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CD200 + cytotoxic T lymphocytes in the tumor microenvironment are crucial for efficacious anti-PD-1/PD-L1 therapy.

Xinxin WangHaoran ZhaWei WuTing YuanShuanglong XieZheng JinHaixia LongFei YangZhongyu WangAnmei ZhangJianbao GaoYing JiangLujing WangChunyan HuYisong Y WanQi-Jing LiAlistair L J SymondsQingzhu JiaBo Zhu
Published in: Science translational medicine (2023)
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.
Keyphrases
  • nk cells
  • primary care
  • transcription factor
  • induced apoptosis
  • oxidative stress
  • single cell
  • regulatory t cells
  • immune response
  • dna damage
  • dendritic cells
  • endoplasmic reticulum stress