The diversity of inhibitory receptor co-expression patterns of exhausted CD8+ T cells in oropharyngeal carcinoma

作者：Yufang Rao, Ke Qiu, Yao Song, Minzi Mao, Lan Feng, Danni Cheng, Junhong Li, Ziyan Zhang, Yuyang Zhang, Xiuli Shao, Wendu Pang, Yan Wang, Xuemei Chen, Chuanhuan Jiang, Sisi Wu, Shuaishuai Yu, Jun Liu, Haiyang Wang, Xingchen Peng, Lin Yang, Li Chen, Xiaosong Mu, Yongbo Zheng, Wei Xu, Geoffrey Liu, Fei Chen, Haopeng Yu, Yu Zhao, Jianjun Ren · 发表于：iScience · 年份：2024 · DOI：10.1016/j.isci.2024.109668 · 被引用次数：1 · 研究领域：Cancer Immunotherapy and Biomarkers、Immune Cell Function and Interaction、CAR-T cell therapy research

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 PDCD1 -based co-expression with other IR genes, whereas dual blockades of PD-1 and cytotoxic T lymphocyte-associated protein 4 (CTLA-4) significantly upregulated CTLA4 -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.