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

Mingjie Lin; Di Chen; Zheyu Shao; Qinyuan Liu; Zhixing Hao; Zhongwei Xin; Yongyuan Chen; Wenxuan Wu; Xiaoke Chen; Teng He; Dang Wu; Pin Wu

doi:10.1016/j.celrep.2024.113767

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

Cell Rep. 2024 Feb 27;43(2):113767. doi: 10.1016/j.celrep.2024.113767. Epub 2024 Feb 13.

Authors

Mingjie Lin¹, Di Chen², Zheyu Shao¹, Qinyuan Liu¹, Zhixing Hao¹, Zhongwei Xin¹, Yongyuan Chen¹, Wenxuan Wu³, Xiaoke Chen¹, Teng He⁴, Dang Wu⁵, Pin Wu⁶

Affiliations

¹ 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.
² 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.
³ 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 Gastrointestinal Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang University, Hangzhou 310009, China.
⁴ 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 Infectious Disease, The Second Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang University, Hangzhou 310009, China.
⁵ 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. Electronic address: [email protected].
⁶ 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. Electronic address: [email protected].

PMID: 38354085
DOI: 10.1016/j.celrep.2024.113767

Abstract

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-1β (IL-1β). 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.

Keywords: CD11b(+)CD4(+) cytotoxic T lymphocytes; CD11b(+)CD4(+)CTLs; CD200R; CP: Cancer; CP: Immunology; DCs; NSCLC; T cell dysfunction; inflammatory dendritic cells; non-small cell lung cancer.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Carcinoma, Non-Small-Cell Lung*
Dendritic Cells
Humans
Lung Neoplasms*
Mice
T-Lymphocytes, Cytotoxic
T-Lymphocytes, Regulatory

Substances

CD200R1 protein, human