Intratumoral PD-1(+)CD8(+) T cells associate poor clinical outcomes and adjuvant chemotherapeutic benefit in gastric cancer.
Intratumoral PD-1(+)CD8(+) T cells associate poor clinical outcomes and adjuvant chemotherapeutic benefit in gastric cancer.
复制标题
瘤内 PD-1 CD8 T 细胞与胃癌不良临床结果和辅助化疗益处相关
DOI：
10.1038/s41416-022-01939-8
复制
发表时间：
2022-11
影响因子：
8.8
通讯作者：
Xu, Jiejie
中科院分区：
文献类型：
--
作者：
Yu, Kuan;Gu, Yun;Zhang, Puran;Fang, Hanji;Cao, Yifan;Wang, Jieti;Lin, Chao;Liu, Hao;Zhang, Heng;He, Hongyong;Li, Ruochen;Qin, Jing;Li, He;Xu, Jiejie
背景
虽然PD-1已被报道为几种恶性肿瘤中T细胞耗竭的标志物，但PD-1+ CD 8 + T细胞在胃癌（GC）中的生物学作用仍不清楚。本研究旨在探讨PD-1+ CD 8 + T细胞在胃癌微环境中的作用及其临床意义。
设计
本研究包括441例肿瘤芯片标本和60例来自中山医院的胃癌患者的流式细胞术标本，以及250例来自亚洲癌症研究组的胃癌患者。
结果
在这里，我们证明PD-1+ CD 8 + T细胞在GC中作为独立的不利因素发挥作用。此外，肿瘤内大量PD-1+ CD 8 + T细胞表明III期GC患者对氟尿嘧啶的化疗反应性较差。从机制上讲，PD-1+ CD 8 + T细胞高浸润表明GC组织中整体CD 8 + T细胞的耗尽表型，其特征在于包括CTLA-4和TIM-3在内的免疫检查点表达升高，而穿孔素表达降低。此外，PD-1+ CD 8 + T细胞高浸润的III期GC患者的几种治疗信号通路的活性升高。
结论
我们的研究强调，PD-1+ CD 8 + T细胞丰度预测GC的预后较差，并可能作为一种新的预测生物标志物来指导治疗选择。
Background
Although PD-1 has been reported to be a marker of T-cell exhaustion in several malignancies, the biological role of PD-1+CD8+ T cells in gastric cancer (GC) remains unclear. Herein, we aimed to investigate the role of PD-1+CD8+ T cells in the tumour microenvironment and its clinical significance in GC.
Designs
This study included 441 tumour microarray specimens and 60 Flow cytometry specimens of GC patients from Zhongshan Hospital, and 250 GC patients from the Asian Cancer Research Group.
Results
Here, we demonstrated that PD-1+CD8+ T cells functioned as an independent adverse prognosticator in GC. In addition, an abundance of intratumoral PD-1+CD8+ T cells indicated worse chemotherapeutic responsiveness to fluorouracil in Stage III GC patients. Mechanistically, PD-1+CD8+ T cell high infiltration indicated an exhausted phenotype of global CD8+ T cells in GC tissues, which was characterised by elevated immune checkpoint expression including CTLA-4 and TIM-3, whereas decreased expression of perforin. Furthermore, PD-1+CD8+ T cell high-infiltration patients with Stage III GC held elevated activity of several therapeutic signal pathways.
Conclusions
Our study highlighted that PD-1+CD8+ T cell abundance predicts inferior prognosis in GC, and may serve as a novel predictive biomarker to guide therapeutic option.
登录
查看更多内容
CXCL13 CD8 T 细胞富集的胃癌患者的临床结果不佳和免疫逃避环境
影响因子：
7.2
作者：
Jin K;Cao Y;Gu Y;Fang H;Fei Y;Wang J;Liu X;Lv K;He X;Lin C;Liu H;Li H;He H;Li R;Zhang H;Xu J
通讯作者：
Xu J
影响因子：
254.7
作者：
Parkin, DM;Bray, F;Pisani, P
通讯作者：
Pisani, P
外周 PD-1( )CD8( ) T 细胞的 TCR 库多样性可预测非小细胞肺癌患者免疫治疗后的临床结果
影响因子：
10.1
作者：
Han, Jiefei;Duan, Jianchun;Wang, Jie
通讯作者：
Wang, Jie
影响因子：
45.3
作者：
Sasako, Mitsuru;Sakuramoto, Shinichi;Ohashi, Yasuo
通讯作者：
Ohashi, Yasuo
影响因子：
82.9
作者：
Cristescu, Razvan;Lee, Jeeyun;Aggarwal, Amit
通讯作者：
Aggarwal, Amit