Inflammatory dendritic cells restrain CD11b+CD4+CTLs via CD200R in human NSCLC

被引：2

作者：

Lin, Mingjie ^{[1
,2
]}

Chen, Di ^{[2
,3
]}

Shao, Zheyu ^{[1
,2
]}

Liu, Qinyuan ^{[1
,2
]}

Hao, Zhixing ^{[1
,2
]}

Xin, Zhongwei ^{[1
,2
]}

Chen, Yongyuan ^{[1
,2
]}

Wu, Wenxuan ^{[2
,4
]}

Chen, Xiaoke ^{[1
,2
]}

He, Teng ^{[2
,5
]}

Wu, Dang ^{[2
]}

Wu, Pin ^{[1
,2
]}

机构：

[1] Zhejiang Univ, Sch Med, Affiliated Hosp 2, Dept Thorac Surg, Hangzhou 310009, Peoples R China

[2] Zhejiang Univ, Sch Med, Affiliated Hosp 2, Key Lab Tumor Microenvironm & Immune Therapy Zheji, Hangzhou, 310009, Peoples R China

[3] Zhejiang Univ, Sch Med, Affiliated Hosp 2, Dept Radiat Oncol, Hangzhou 310009, Peoples R China

[4] Zhejiang Univ, Affiliated Hosp 2, Sch Med, Dept Gastrointestinal Surg, Hangzhou 310009, Peoples R China

[5] Zhejiang Univ, Sch Med, Affiliated Hosp 2, Dept Infect Dis, Hangzhou 310009, Peoples R China

来源：

CELL REPORTS | 2024年 / 43卷 / 02期

基金：

中国国家自然科学基金;

关键词：

CD4(+) T-CELLS; RESIDENT MEMORY; LYMPHOCYTES; EXPRESSION; TISSUE; MELANOMA; HELPER;

D O I：

10.1016/j.celrep.2024.113767

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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 CD11b+CD4+ CTLs as a cytotoxic subset of CD4+ T cells in multiple tissues of NSCLC patients. In addition, tumor -infiltrating CD11b+CD4+ 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 CD11b+CD4+ CTLs via CD200. Mechanistically, inflammatory dendritic cells promote the CD200R expression of CD11b+CD4+ CTLs by secreting interleukin-1b (IL -1b). Finally, we demonstrate that CD200 blockade can revive the tumor -killing role of CD11b+CD4+ CTLs and prolong the survival of tumor -bearing mice. Taken together, our study identifies CD11b+CD4+ CTLs in NSCLC with decreased cytotoxicity that can be reinvigorated by CD200 blockade, suggesting that targeting CD200 is a promising immunotherapy strategy in NSCLC.

引用

页数：22

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