Dataset Information

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

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.

SUBMITTER: Ao YQ

PROVIDER: S-EPMC10120154 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature

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Publications

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

Ao Yong-Qiang YQ Gao Jian J Zhang Ling-Xian LX Deng Jie J Wang Shuai S Lin Miao M Wang Hai-Kun HK Ding Jian-Yong JY Jiang Jia-Hao JH

BMC cancer 20230421 1

<h4>Background</h4>The scavenger receptor CD36 was reported to be highly expressed on tumor-infiltrating CD8<sup>+</sup> T cells, but the clinical role remains obscure. This study aims to explore the infiltration and clinical value of CD36<sup>+</sup>CD8<sup>+</sup> T cells in NSCLC.<h4>Methods</h4>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 a ...[more]

PMID: 37085798

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Project description:Background and aimsTargeting costimulatory receptors with agonistic antibodies is a promising cancer immunotherapy option. We aimed to investigate costimulatory receptor expression, particularly 4-1BB (CD137 or tumor necrosis factor receptor superfamily member 9), on tumor-infiltrating CD8+ T cells (CD8+ tumor-infiltrating lymphocytes [TILs]) and its association with distinct T-cell activation features among exhausted CD8+ TILs in hepatocellular carcinoma (HCC).Approach and resultsTumor tissues, adjacent nontumor tissues, and peripheral blood were collected from HCC patients undergoing surgical resection (n = 79). Lymphocytes were isolated and used for multicolor flow cytometry, RNA-sequencing, and in vitro functional restoration assays. Among the examined costimulatory receptors, 4-1BB was most prominently expressed on CD8+ TILs. 4-1BB expression was almost exclusively detected on CD8+ T cells in the tumor-especially on programmed death 1 (PD-1)high cells and not PD-1int and PD-1neg cells. Compared to PD-1int and 4-1BBneg PD-1high CD8+ TILs, 4-1BBpos PD-1high CD8+ TILs exhibited higher levels of tumor reactivity and T-cell activation markers and significant enrichment for T-cell activation gene signatures. Per-patient analysis revealed positive correlations between percentages of 4-1BBpos cells among CD8+ TILs and levels of parameters of tumor reactivity and T-cell activation. Among highly exhausted PD-1high CD8+ TILs, 4-1BBpos cells harbored higher proportions of cells with proliferative and reinvigoration potential. Our 4-1BB-related gene signature predicted survival outcomes of HCC patients in the The Cancer Genome Atlas cohort. 4-1BB agonistic antibodies enhanced the function of CD8+ TILs and further enhanced the anti-PD-1-mediated reinvigoration of CD8+ TILs, especially in cases showing high levels of T-cell activation.Conclusion4-1BB expression on CD8+ TILs represents a distinct activation state among highly exhausted CD8+ T cells in HCC. 4-1BB costimulation with agonistic antibodies may be a promising strategy for treating HCCs exhibiting prominent T-cell activation.

Dataset Information

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

Background

Methods

Results

Conclusion

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Dataset Information

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

Background

Methods

Results

Conclusion

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

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