Rao Yufang, Qiu Ke, Song Yao, Mao Minzi, Feng Lan, Cheng Danni, Li Junhong, Zhang Ziyan, Zhang Yuyang, Shao Xiuli, Pang Wendu, Wang Yan, Chen Xuemei, Jiang Chuanhuan, Wu Sisi, Yu Shuaishuai, Liu Jun, Wang Haiyang, Peng Xingchen, Yang Lin, Chen Li, Mu Xiaosong, Zheng Yongbo, Xu Wei, Liu Geoffrey, Chen Fei, Yu Haopeng, Zhao Yu, Ren Jianjun
Department of Otolaryngology-Head & Neck Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
Research Core Facility of West China Hospital, Sichuan University, Chengdu, China.
iScience. 2024 Apr 5;27(5):109668. doi: 10.1016/j.isci.2024.109668. eCollection 2024 May 17.
Exhausted CD8 T cells (Texs) are characterized by the expression of various inhibitory receptors (IRs), whereas the functional attributes of these co-expressed IRs remain limited. Here, we systematically characterized the diversity of IR co-expression patterns in Texs from both human oropharyngeal squamous cell carcinoma (OPSCC) tissues and syngeneic OPSCC model. Nearly 60% of the Texs population co-expressed two or more IRs, and the number of co-expressed IRs was positively associated with superior exhaustion and cytotoxicity phenotypes. In OPSCC patients, programmed cell death-1 (PD-1) blockade significantly enhanced -based co-expression with other IR genes, whereas dual blockades of PD-1 and cytotoxic T lymphocyte-associated protein 4 (CTLA-4) significantly upregulated -based co-expression with other IR genes. Collectively, our findings demonstrate that highly diverse IR co-expression is a leading feature of Texs and represents their functional states, which might provide essential clues for the rational selection of immune checkpoint inhibitors in treating OPSCC.
耗竭的CD8 T细胞（Texs）以多种抑制性受体（IRs）的表达为特征，然而这些共表达的IRs的功能特性仍然有限。在此，我们系统地描述了来自人类口咽鳞状细胞癌（OPSCC）组织和同基因OPSCC模型的Texs中IR共表达模式的多样性。近60%的Texs群体共表达两种或更多种IRs，并且共表达的IRs数量与更高的耗竭和细胞毒性表型呈正相关。在OPSCC患者中，程序性细胞死亡蛋白1（PD-1）阻断显著增强了与其他IR基因的共表达，而PD-1和细胞毒性T淋巴细胞相关蛋白4（CTLA-4）的双重阻断显著上调了与其他IR基因的共表达。总的来说，我们的研究结果表明，高度多样的IR共表达是Texs的一个主要特征，并代表了它们的功能状态，这可能为合理选择免疫检查点抑制剂治疗OPSCC提供重要线索。
