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  3. Tumor-infiltrating CD36+CD8+T cells determine exhausted tumor microenvironment and correlate with inferior response to chemotherapy in non-small cell lung cancer

Tumor-infiltrating CD36+CD8+T cells determine exhausted tumor microenvironment and correlate with inferior response to chemotherapy in non-small cell lung cancer

  • BMC Cancer. 2023 Apr 21;23(1):367. doi: 10.1186/s12885-023-10836-z.
Yong-Qiang Ao # 1 2,  Jian Gao # 1 2,  Ling-Xian Zhang # 3,  Jie Deng 4,  Shuai Wang 1 2,  Miao Lin 1 2,  Hai-Kun Wang 5,  Jian-Yong Ding 6 7,  Jia-Hao Jiang 8 9
Affiliations

Affiliations

  • 1 Department of Thoracic Surgery, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai, 200032, P. R. China.
  • 2 Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, China.
  • 3 Department of Cardiothoracic Surgery, the Second Affiliated Hospital of Nanchang University, Nanchang, 330000, P.R. China.
  • 4 Institute of Vascular Disease, Shanghai TCM-Integrated Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
  • 5 CAS Key Laboratory of Molecular Virology and Immunology, Institute Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, China.
  • 6 Department of Thoracic Surgery, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai, 200032, P. R. China. ding.jianyong@zs-hospital.sh.cn.
  • 7 Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, China. ding.jianyong@zs-hospital.sh.cn.
  • 8 Department of Thoracic Surgery, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai, 200032, P. R. China. jiang.jiahao@zs-hospital.sh.cn.
  • 9 Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, China. jiang.jiahao@zs-hospital.sh.cn.
  • # Contributed equally.
PMID: 37085798 DOI: 10.1186/s12885-023-10836-z
Abstract

Background: The scavenger receptor CD36 was reported to be highly expressed on tumor-infiltrating CD8+ T cells, but the clinical role remains obscure. This study aims to explore the infiltration and clinical value of CD36+CD8+ T cells in NSCLC.

Methods: Immunohistochemistry and immunofluorescence were conducted for survival analyses and immunological evaluation in 232 NSCLC patients in Zhongshan Hospital. Flow cytometry analyses were carried out to assess the immune cells from fresh tumor samples, non-tumor tissues and peripheral blood. In vitro tumor infiltrating lymphocytes cultures were conducted to test the effect of CD36 blockage.

Results: Accumulation of CD36+CD8+ T cells in tumor tissues was correlated with more advanced stage (p < 0.001), larger tumor size (p < 0.01), and lymph node metastasis (p < 0.0001) in NSCLC. Moreover, high infiltration of CD36+CD8+ T cells indicated poor prognosis in terms of both overall survival (OS) and recurrence-free survival (RFS) and inferior chemotherapy response. CD36+CD8+ T cells showed decreased GZMB (p < 0.0001) and IFN-γ (p < 0.001) with elevated PD-1 (p < 0.0001) and TIGIT (p < 0.0001). Analysis of tumor-infiltrating immune cell landscape revealed a positive correlation between CD36+CD8+ T cells and Tregs (p < 0.01) and M2-polarized macrophages (p < 0.01) but a negative correlation with Th1 (p < 0.05). Notably, inhibition of CD36 partially restored the cytotoxic function of CD8+ T cells by producing more GZMB and IFN-γ.

Conclusion: CD36+CD8+ T cells exhibit impaired immune function and high infiltration of CD36+CD8+ T cells indicated poor prognosis and inferior chemotherapy response in NSCLC patients. CD36 could be a therapeutic target in combination with chemotherapy in NSCLC patients.

Keywords

CD36+CD8+ T cells; Chemotherapy; NSCLC; Prognosis; Tumor microenvironment.

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