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

Author:

Wang Xinxin1ORCID,Zha Haoran12ORCID,Wu Wei3,Yuan Ting1,Xie Shuanglong1,Jin Zheng4,Long Haixia1ORCID,Yang Fei1,Wang Zhongyu1,Zhang Anmei1,Gao Jianbao1ORCID,Jiang Ying2ORCID,Wang Lujing1,Hu Chunyan1,Wan Yisong Y.5ORCID,Li Qi-Jing6ORCID,Symonds Alistair L. J.7ORCID,Jia Qingzhu1ORCID,Zhu Bo1ORCID

Affiliation:

1. Institute of Cancer, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, P. R. China.

2. 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. Research Institute, GloriousMed Clinical Laboratory (Shanghai) Co. Ltd., 201318, P. R. China.

5. Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.

6. Department of Immunology, Duke University Medical Center, Durham, NC 27710, USA.

7. Blizard Institute, Barts and London School of Medicine and Dentistry, University of London, London, E1 2AT UK.

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.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

General Medicine

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3