eLife (Feb 2023)
Proliferative exhausted CD8+ T cells exacerbate long-lasting anti-tumor effects in human papillomavirus-positive head and neck squamous cell carcinoma
- Danni Cheng,
- Ke Qiu,
- Yufang Rao,
- Minzi Mao,
- Li Li,
- Yan Wang,
- Yao Song,
- Junren Chen,
- Xiaowei Yi,
- Xiuli Shao,
- Shao Hui Huang,
- Yi Zhang,
- Xuemei Chen,
- Sisi Wu,
- Shuaishuai Yu,
- Jun Liu,
- Haiyang Wang,
- Xingchen Peng,
- Daibo Li,
- Lin Yang,
- Li Chen,
- Zhiye Ying,
- Yongbo Zheng,
- Meijun Zheng,
- Binwu Ying,
- Xiaoxi Zeng,
- Wei Zhang,
- Wei Xu,
- Geoffrey Liu,
- Fei Chen,
- Haopeng Yu,
- Yu Zhao,
- Jianjun Ren
Affiliations
- Danni Cheng
- ORCiD
- Department of Oto-Rhino-Laryngology, and National Clinical Research Center for Geriatrics, West China Hospital, West China Medical School, Sichuan University, Chengdu, China
- Ke Qiu
- Department of Oto-Rhino-Laryngology, and National Clinical Research Center for Geriatrics, West China Hospital, West China Medical School, Sichuan University, Chengdu, China
- Yufang Rao
- Department of Oto-Rhino-Laryngology, and National Clinical Research Center for Geriatrics, West China Hospital, West China Medical School, Sichuan University, Chengdu, China
- Minzi Mao
- ORCiD
- Department of Oto-Rhino-Laryngology, and National Clinical Research Center for Geriatrics, West China Hospital, West China Medical School, Sichuan University, Chengdu, China
- Li Li
- Institute of Clinical Pathology, West China Hospital, Sichuan University, Chengdu, China
- Yan Wang
- Research Core Facility of West China Hospital, Sichuan University, Chengdu, China
- Yao Song
- Department of Oto-Rhino-Laryngology, and National Clinical Research Center for Geriatrics, West China Hospital, West China Medical School, Sichuan University, Chengdu, China
- Junren Chen
- West China Biomedical Big Data Center, West China Hospital, Sichuan University, Chengdu, China
- Xiaowei Yi
- Department of Oto-Rhino-Laryngology, and National Clinical Research Center for Geriatrics, West China Hospital, West China Medical School, Sichuan University, Chengdu, China
- Xiuli Shao
- Department of Oto-Rhino-Laryngology, and National Clinical Research Center for Geriatrics, West China Hospital, West China Medical School, Sichuan University, Chengdu, China
- Shao Hui Huang
- Department of Radiation Oncology, Princess Margaret Cancer Centre, University of Toronto, Toronto, Canada
- Yi Zhang
- Research Core Facility of West China Hospital, Sichuan University, Chengdu, China
- Xuemei Chen
- 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 Oto-Rhino-Laryngology, and National Clinical Research Center for Geriatrics, West China Hospital, West China Medical School, Sichuan University, Chengdu, China
- Haiyang Wang
- Department of Oto-Rhino-Laryngology, and National Clinical Research Center for Geriatrics, West China Hospital, West China Medical School, Sichuan University, Chengdu, China
- Xingchen Peng
- Department of Biotherapy and National Clinical Research Center for Geriatrics, Cancer Center, West China Hospital, Sichuan University, Chengdu, China
- Daibo Li
- Department of Oto-Rhino-Laryngology, and National Clinical Research Center for Geriatrics, West China Hospital, West China Medical School, Sichuan University, Chengdu, China
- Lin Yang
- MinSheng Ear-Nose-Throat Hospital, Chengdu, China
- Li Chen
- MinSheng Ear-Nose-Throat Hospital, Chengdu, China
- Zhiye Ying
- West China Biomedical Big Data Center, West China Hospital, Sichuan University, Chengdu, China
- Yongbo Zheng
- Department of Oto-Rhino-Laryngology, and National Clinical Research Center for Geriatrics, West China Hospital, West China Medical School, Sichuan University, Chengdu, China
- Meijun Zheng
- Department of Oto-Rhino-Laryngology, and National Clinical Research Center for Geriatrics, West China Hospital, West China Medical School, Sichuan University, Chengdu, China
- Binwu Ying
- Department of Oto-Rhino-Laryngology, and National Clinical Research Center for Geriatrics, West China Hospital, West China Medical School, Sichuan University, Chengdu, China; Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu, China
- Xiaoxi Zeng
- Department of Oto-Rhino-Laryngology, and National Clinical Research Center for Geriatrics, West China Hospital, West China Medical School, Sichuan University, Chengdu, China; West China Biomedical Big Data Center, West China Hospital, Sichuan University, Chengdu, China
- Wei Zhang
- Institute of Clinical Pathology, West China Hospital, Sichuan University, Chengdu, China
- Wei Xu
- Department of Biostatistics, Princess Margaret Cancer Centre and Dalla Lana School of Public Health, Toronto, Canada
- Geoffrey Liu
- Department of Medicine, Division of Medical Oncology and Hematology, Princess Margaret Cancer Center, University Health Network, University of Toronto, Toronto, Canada
- Fei Chen
- Department of Oto-Rhino-Laryngology, and National Clinical Research Center for Geriatrics, West China Hospital, West China Medical School, Sichuan University, Chengdu, China
- Haopeng Yu
- Department of Oto-Rhino-Laryngology, and National Clinical Research Center for Geriatrics, West China Hospital, West China Medical School, Sichuan University, Chengdu, China; West China Biomedical Big Data Center, West China Hospital, Sichuan University, Chengdu, China
- Yu Zhao
- ORCiD
- Department of Oto-Rhino-Laryngology, and National Clinical Research Center for Geriatrics, West China Hospital, West China Medical School, Sichuan University, Chengdu, China; West China Biomedical Big Data Center, West China Hospital, Sichuan University, Chengdu, China
- Jianjun Ren
- ORCiD
- Department of Oto-Rhino-Laryngology, and National Clinical Research Center for Geriatrics, West China Hospital, West China Medical School, Sichuan University, Chengdu, China; West China Biomedical Big Data Center, West China Hospital, Sichuan University, Chengdu, China
- DOI
- https://doi.org/10.7554/eLife.82705
- Journal volume & issue
-
Vol. 12
Abstract
The survival prognosis of human papillomavirus (HPV)-positive and HPV-negative head and neck squamous cell carcinoma (HNSCC) is largely different, and little is known about the anti-tumor mechanism of tumor-infiltrated exhausted CD8+ T cells (Tex) in HNSCC. We performed cell-level multi-omics sequencing on human HNSCC samples to decipher the multi-dimensional characteristics of Tex cells. A proliferative exhausted CD8+ T cell cluster (P-Tex) which was beneficial to survival outcomes of patients with HPV-positive HNSCC was identified. Interestingly, P-Tex cells expressed CDK4 genes as high as cancer cells, which could be simultaneously inhibited by CDK4 inhibitors and might be a potential reason for the ineffectiveness of CDK4 inhibitors in treating HPV-positive HNSCC. P-Tex cells could aggregate in the antigen-presenting cell niches and activate certain signaling pathways. Together, our findings suggest a promising role for P-Tex cells in the prognosis of patients with HPV-positive HNSCC by providing modest but persistent anti-tumor effects.
Keywords
- tumor microenvironment
- human papillomavirus
- CDK4 inhibitor
- proliferative exhausted CD8+ T cells
- head and neck squamous cell carcinoma
