一种用于克服非小细胞肺癌治疗中抗原异质性的多靶向 CAR-T 细胞平台
A Multi-Targeting Chimeric Antigen Receptor-T Cell Platform to Overcome Antigen Heterogeneity in the Treatment of Non-Small Cell Lung Cancer.
这些发现支持采用多靶点CAR-T 策略来应对NSCLC及可能其他实体瘤中的抗原异质性。
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
肿瘤浸润性 CD36(+)CD8(+)T 细胞决定耗竭的肿瘤微环境，并与非小细胞肺癌化疗反应较差相关
英文原题：Tumor-infiltrating CD36(+)CD8(+)T cells determine exhausted tumor microenvironment and correlate with inferior response to chemotherapy in non-small cell lung cancer.
查看英文原题
Tumor-infiltrating CD36(+)CD8(+)T cells determine exhausted tumor microenvironment and correlate with inferior response to chemotherapy in non-small cell lung cancer.
分数与星级只用于站内排序 —— 不代表疗效、安全性或个人适用性。
研究概要
CD36 + CD8 + T 细胞表现出免疫功能受损，CD36 + CD8 + T 细胞高浸润提示 NSCLC 患者预后不良且化疗反应较差。CD36 可能成为 NSCLC 患者联合化疗的治疗靶点。
研究思路结论见上方概要
背景
清道夫受体 CD36 被报道在肿瘤浸润性 CD8 + T 细胞上高表达，但其临床作用仍不清楚。本研究旨在探讨 CD36 + CD8 + T 细胞在 NSCLC 中的浸润情况及临床价值。
方法
在中山医院的232例NSCLC患者中，进行了免疫组织化学和免疫荧光检测以进行生存分析和免疫学评估。采用流式细胞术分析评估来自新鲜肿瘤样本、非肿瘤组织和外周血的免疫细胞。进行了体外TIL（肿瘤浸润淋巴细胞）培养以测试CD36阻断的效果。
结果
CD36 + CD8 + T细胞在肿瘤组织中的积聚与NSCLC更晚的临床分期（p < 0.001）、更大的肿瘤体积（p < 0.01）和淋巴结转移（p < 0.0001）相关。此外，CD36 + CD8 + T细胞高浸润提示总生存期（OS）和无复发生存期（RFS）预后不良，且化疗反应较差。CD36 + CD8 + T细胞表现为GZMB（p < 0.0001）和IFN-γ（p < 0.001）降低，同时PD-1（p < 0.0001）和TIGIT（p < 0.0001）升高。对肿瘤浸润免疫细胞图谱的分析显示，CD36 + CD8 + T细胞与Tregs（p < 0.01）和M2极化巨噬细胞（p < 0.01）呈正相关，但与Th1（p < 0.05）呈负相关。值得注意的是，抑制CD36可通过产生更多的GZMB和IFN-γ部分恢复CD8 + T细胞的细胞毒性功能。
展开英文摘要原文
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.
论文信息
- 作者
- Ao YQ、Gao J、Zhang LX、Deng J、Wang S、Lin M、Wang HK、Ding JY
- 第一作者单位
- Department of Thoracic Surgery, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai, 200032, P. R. China.China
- 通讯作者单位
- Department of Thoracic Surgery, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai, 200032, P. R. China. jiang.jiahao@zs-hospital.sh.cn.China
- 期刊
- BMC cancer2023 Apr 21
- 原文标识
- PubMed 37085798 · DOI 10.1186/s12885-023-10836-z
在 PubMed 查看 → 出版商原文（DOI） 全文 PDF（PMC）· 可下载 治疗专题与资料阅读指南 资料来源与翻译说明 报告译文或资料问题 →