肿瘤浸润的CD36+CD8+T细胞决定了疲惫的肿瘤微环境,并与非小细胞肺癌化疗的劣异反应相关。
Tumor-infiltrating CD36+CD8+T cells determine exhausted tumor microenvironment and correlate with inferior response to chemotherapy in non-small cell lung cancer.
发表日期:2023 Apr 21
作者:
Yong-Qiang Ao, Jian Gao, Ling-Xian Zhang, Jie Deng, Shuai Wang, Miao Lin, Hai-Kun Wang, Jian-Yong Ding, Jia-Hao Jiang
来源:
Immunity & Ageing
摘要:
CD36清道夫受体被报告在浸润肿瘤的CD8+ T细胞中高表达,但其临床作用仍不明确。本研究旨在探讨NSCLC患者中CD36+ CD8+ T细胞的浸润和临床价值。在中山医院的232名NSCLC患者中进行免疫组化和免疫荧光分析,并进行生存分析和免疫学评估。进行流式细胞仪分析以评估来自新鲜肿瘤样本、非肿瘤组织和外周血的免疫细胞。进行离体肿瘤浸润淋巴细胞培养以测试CD36阻断的效果。在NSCLC的肿瘤组织中,CD36+ CD8+ T细胞的积累与更进阶的阶段(p < 0.001)、更大的肿瘤大小(p < 0.01)和淋巴结转移(p < 0.0001)相关。此外,CD36+ CD8+ T细胞的高浸润程度预示着存活率和无复发生存率的不良预后以及劣质化疗反应。CD36+ CD8+ T细胞显示出降低的GZMB(p < 0.0001)和IFN-γ(p < 0.001)以及升高的PD-1(p < 0.0001)和TIGIT(p < 0.0001)。肿瘤浸润免疫细胞景观的分析揭示了CD36+ CD8+ T细胞与Tregs(p < 0.01)和M2极化的巨噬细胞(p < 0.01)之间的正相关,但与Th1(p < 0.05)呈负相关。值得注意的是,CD36的抑制部分恢复了CD8+ T细胞的细胞毒素功能,产生更多的GZMB和IFN-γ。CD36+ CD8+ T细胞表现出免疫功能受损,CD36+ CD8+ T细胞的高浸润程度提示NSCLC患者的不良预后和劣质化疗反应。CD36可能成为与NSCLC患者化疗相结合的治疗靶点。©2023年作者。
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.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.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.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.© 2023. The Author(s).