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

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

doi:10.1016/j.isci.2024.109668

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

iScience. 2024 Apr 5;27(5):109668. doi: 10.1016/j.isci.2024.109668. eCollection 2024 May 17.

Authors

Yufang Rao¹, Ke Qiu¹, Yao Song¹, Minzi Mao¹, Lan Feng¹, Danni Cheng¹, Junhong Li¹, Ziyan Zhang¹, Yuyang Zhang¹, Xiuli Shao¹, Wendu Pang¹, Yan Wang², Xuemei Chen², Chuanhuan Jiang², Sisi Wu², Shuaishuai Yu², Jun Liu¹, Haiyang Wang¹, Xingchen Peng³, Lin Yang⁴, Li Chen⁴, Xiaosong Mu⁵, Yongbo Zheng¹, Wei Xu⁶, Geoffrey Liu^{7

8}, Fei Chen¹, Haopeng Yu⁹, Yu Zhao¹, Jianjun Ren¹

Affiliations

¹ Department of Otolaryngology-Head & Neck Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
² Research Core Facility of West China Hospital, Sichuan University, Chengdu, China.
³ Department of Biotherapy and National Clinical Research Center for Geriatrics, Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
⁴ MinSheng Ear-Nose-Throat Hospital, Chengdu, Sichuan, China.
⁵ Langzhong People's Hospital, Nanchong, Sichuan, China.
⁶ Department of Biostatistics, Princess Margaret Cancer Centre and Dalla Lana School of Public Health, Toronto, ON, Canada.
⁷ Medical Oncology and Hematology, Princess Margaret Cancer Centre, and Department of Medicine, University of Toronto, Toronto, ON, Canada.
⁸ Department of Medicine, Division of Medical Oncology and Hematology, Princess Margaret Cancer Center, University Health Network, University of Toronto, Toronto, ON, Canada.
⁹ West China Biomedical Big Data Center, West China Hospital, Sichuan University, Chengdu, China.

Abstract

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.

Keywords: Cancer; Immunology.