iScience (May 2024)
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
Affiliations
- Yufang Rao
- Department of Otolaryngology-Head & Neck Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan, China
- Ke Qiu
- Department of Otolaryngology-Head & Neck Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan, China
- Yao Song
- Department of Otolaryngology-Head & Neck Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan, China
- Minzi Mao
- Department of Otolaryngology-Head & Neck Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan, China
- Lan Feng
- Department of Otolaryngology-Head & Neck Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan, China
- Danni Cheng
- Department of Otolaryngology-Head & Neck Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan, China
- Junhong Li
- Department of Otolaryngology-Head & Neck Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan, China
- Ziyan Zhang
- Department of Otolaryngology-Head & Neck Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan, China
- Yuyang Zhang
- Department of Otolaryngology-Head & Neck Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan, China
- Xiuli Shao
- Department of Otolaryngology-Head & Neck Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan, China
- Wendu Pang
- Department of Otolaryngology-Head & Neck Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan, China
- Yan Wang
- Research Core Facility of West China Hospital, Sichuan University, Chengdu, China
- Xuemei Chen
- Research Core Facility of West China Hospital, Sichuan University, Chengdu, China
- Chuanhuan Jiang
- Research Core Facility of West China Hospital, Sichuan University, Chengdu, China
- Sisi Wu
- Research Core Facility of West China Hospital, Sichuan University, Chengdu, China
- Shuaishuai Yu
- Research Core Facility of West China Hospital, Sichuan University, Chengdu, China
- Jun Liu
- Department of Otolaryngology-Head & Neck Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan, China
- Haiyang Wang
- Department of Otolaryngology-Head & Neck Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan, China
- Xingchen Peng
- Department of Biotherapy and National Clinical Research Center for Geriatrics, Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China
- Lin Yang
- MinSheng Ear-Nose-Throat Hospital, Chengdu, Sichuan, China
- Li Chen
- MinSheng Ear-Nose-Throat Hospital, Chengdu, Sichuan, China
- Xiaosong Mu
- Langzhong People’s Hospital, Nanchong, Sichuan, China
- Yongbo Zheng
- Department of Otolaryngology-Head & Neck Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan, China
- Wei Xu
- Department of Biostatistics, Princess Margaret Cancer Centre and Dalla Lana School of Public Health, Toronto, ON, Canada
- Geoffrey Liu
- Medical Oncology and Hematology, Princess Margaret Cancer Centre, and Department of Medicine, University of Toronto, Toronto, ON, Canada; Department of Medicine, Division of Medical Oncology and Hematology, Princess Margaret Cancer Center, University Health Network, University of Toronto, Toronto, ON, Canada
- Fei Chen
- Department of Otolaryngology-Head & Neck Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan, China
- Haopeng Yu
- West China Biomedical Big Data Center, West China Hospital, Sichuan University, Chengdu, China
- Yu Zhao
- Department of Otolaryngology-Head & Neck Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan, China; Corresponding author
- Jianjun Ren
- Department of Otolaryngology-Head & Neck Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan, China; Corresponding author
- Journal volume & issue
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Vol. 27,
no. 5
p. 109668
Abstract
Summary: 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.
