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BMC Cancer
Published in: BMC Cancer 1/2023

Open Access 01-12-2023 | NSCLC | Research

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

Authors: Yong-Qiang Ao, Jian Gao, Ling-Xian Zhang, Jie Deng, Shuai Wang, Miao Lin, Hai-Kun Wang, Jian-Yong Ding, Jia-Hao Jiang

Published in: BMC Cancer | Issue 1/2023

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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.
Appendix
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Metadata
Title
Tumor-infiltrating CD36+CD8+T cells determine exhausted tumor microenvironment and correlate with inferior response to chemotherapy in non-small cell lung cancer
Authors
Yong-Qiang Ao
Jian Gao
Ling-Xian Zhang
Jie Deng
Shuai Wang
Miao Lin
Hai-Kun Wang
Jian-Yong Ding
Jia-Hao Jiang
Publication date
01-12-2023
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2023
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-023-10836-z

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