在人类非小细胞肺癌中，炎性树突状细胞通过CD200R抑制CD11bCD4细胞毒性T淋巴细胞。
Inflammatory dendritic cells restrain CD11bCD4 CTLs via CD200R in human NSCLC.
作者信息
Lin Mingjie, Chen Di, Shao Zheyu, Liu Qinyuan, Hao Zhixing, Xin Zhongwei, Chen Yongyuan, Wu Wenxuan, Chen Xiaoke, He Teng, Wu Dang, Wu Pin
机构信息
Department of Thoracic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang University, Hangzhou 310009, China; Key Laboratory of Tumor Microenvironment and Immune Therapy of Zhejiang Province, The Second Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang University, Hangzhou 310009, China.
Key Laboratory of Tumor Microenvironment and Immune Therapy of Zhejiang Province, The Second Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang University, Hangzhou 310009, China; Department of Radiation Oncology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang University, Hangzhou 310009, China.
出版信息
Cell Rep. 2024 Feb 27;43(2):113767. doi: 10.1016/j.celrep.2024.113767. Epub 2024 Feb 13.
CD4 cytotoxic T lymphocytes (CD4 CTLs) are suggested to play a crucial role in inflammatory diseases, including cancer, but their characteristics in human non-small cell lung cancer (NSCLC) remain unknown. Here, using the cell surface marker CD11b, we identify CD11bCD4 CTLs as a cytotoxic subset of CD4 T cells in multiple tissues of NSCLC patients. In addition, tumor-infiltrating CD11bCD4 CTLs show a dysfunctional phenotype with elevated expression of CD200 receptor (CD200R), a negatively immunomodulatory receptor. CD4 regulatory T (Treg) cells restrain the anti-tumor role of CD11bCD4 CTLs via CD200. Mechanistically, inflammatory dendritic cells promote the CD200R expression of CD11bCD4 CTLs by secreting interleukin-1β (IL-1β). Finally, we demonstrate that CD200 blockade can revive the tumor-killing role of CD11bCD4 CTLs and prolong the survival of tumor-bearing mice. Taken together, our study identifies CD11bCD4 CTLs in NSCLC with decreased cytotoxicity that can be reinvigorated by CD200 blockade, suggesting that targeting CD200 is a promising immunotherapy strategy in NSCLC.
CD4细胞毒性T淋巴细胞（CD4 CTLs）被认为在包括癌症在内的炎症性疾病中起关键作用，但其在人类非小细胞肺癌（NSCLC）中的特征仍不清楚。在这里，我们利用细胞表面标志物CD11b，在NSCLC患者的多个组织中鉴定出CD11bCD4 CTLs是CD4 T细胞的一个细胞毒性亚群。此外，肿瘤浸润的CD11bCD4 CTLs表现出功能失调的表型，其负性免疫调节受体CD200受体（CD200R）表达升高。CD4调节性T（Treg）细胞通过CD200抑制CD11bCD4 CTLs的抗肿瘤作用。机制上，炎性树突状细胞通过分泌白细胞介素-1β（IL-1β）促进CD11bCD4 CTLs的CD200R表达。最后，我们证明CD200阻断可以恢复CD11bCD4 CTLs的肿瘤杀伤作用，并延长荷瘤小鼠的生存期。综上所述，我们的研究在NSCLC中鉴定出具有降低细胞毒性的CD11bCD4 CTLs，其可通过CD200阻断而恢复活力，这表明靶向CD200是NSCLC中一种有前景的免疫治疗策略。
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