Distribution, phenotype, functional and clinical relevance of CD8(+)CD103(+) tissue-resident memory T cells in human gastric cancer.
Distribution, phenotype, functional and clinical relevance of CD8(+)CD103(+) tissue-resident memory T cells in human gastric cancer.
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人胃癌中 CD8( )CD103( ) 组织驻留记忆 T 细胞的分布、表型、功能和临床相关性。
DOI：
10.1007/s00262-021-03105-0
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发表时间：
2021
期刊：
影响因子：
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通讯作者：
Peng Liu-Sheng
中科院分区：
文献类型：
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作者：
Shen Yang;Li Xiao-Long;Li Yu-Xian;Shan Zhi-Guo;Zhao Yong-Liang;Cheng Ping;Zhao Zhuo;Zhang Jin-Yu;Chen Weisan;Zhuang Yuan;Ma Dai-Yuan;Zou Quan-Ming;Qiu Yuan;Peng Liu-Sheng
CD8+CD103+组织驻留记忆T细胞（TRMs）参与肿瘤免疫应答，并与人类癌症的良好临床结果相关。然而，这些细胞在胃癌（GC）中的分布、表型、功能特性和临床相关性尚不清楚。在这里，我们的数据显示，与非肿瘤组织相比，肿瘤中CD8+CD103+ trm的百分比显着降低。大多数肿瘤浸润的CD8+CD103+TRMs是CD45RA - CCR7 -效应记忆细胞，PD-1和4-1BB的表达高于非肿瘤组织。此外，肿瘤浸润的CD8+CD103+TRMs由于颗粒酶B和穿孔素表达降低而显示出细胞溶解能力受损。此外，体外PD-1阻断可以恢复肿瘤浸润的CD8+CD103+TRMs的细胞溶解能力，并且这种抗PD-1介导的CD8+CD103+TRMs的再生可以通过4-1BB共刺激进一步增强。最后，较低水平的肿瘤浸润性CD8+CD103+TRMs与GC进展和不良患者生存呈正相关。我们的数据表明，通过结合PD-1阻断和4-1BB共刺激来恢复CD8+CD103+TRM功能可能是治疗GC的一种有希望的策略。
CD8+CD103+tissue-resident memory T cells (TRMs) are involved in tumor immune response and linked to favorable clinical outcome in human cancer. However, the distribution, phenotype, functional properties and clinical relevance of these cells in gastric cancer (GC) remain elusive. Here, our data show that, in comparison to non-tumor tissues, the percentages of CD8+CD103+TRMs in tumors are significantly decreased. Most tumor-infiltrating CD8+CD103+TRMs are CD45RA−CCR7−effector-memory cells with higher PD-1 and 4-1BB expression than those from non-tumor tissues. Further, tumor-infiltrating CD8+CD103+TRMs show impaired cytolytic capacity due to decreased granzyme B and perforin expression. Moreover, ex vivo PD-1 blockade could restore the cytolytic capacity of tumor-infiltrating CD8+CD103+TRMs, and such anti-PD-1-mediated reinvigoration of CD8+CD103+TRMs could be further enhanced by 4-1BB co-stimulation. Finally, lower levels of Tumor-infiltrating CD8+CD103+TRMs are positively correlated with GC progression and poor patients’ survival. Our data suggest that restoring CD8+CD103+TRM function by combining PD-1 blockade and 4-1BB co-stimulation may be a promising strategy for treating GC.