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Proliferative exhausted CD8+ T cells exacerbate long-lasting anti-tumor effects in human papillomavirus-positive head and neck squamous cell carcinoma

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机构： [1]Department of Oto-Rhino-Laryngology, and National Clinical Research Center for Geriatrics, West China Hospital, West China Medical School, Sichuan University, Chengdu, China. [2]Institute of Clinical Pathology, West China Hospital, Sichuan University, Chengdu, China. [3]Research Core Facility of West China Hospital, Sichuan University, Chengdu, China. [4]West China Biomedical Big Data Center, West China Hospital, Sichuan University, Chengdu, China. [5]Department of Radiation Oncology, Princess Margaret Cancer Centre, University of Toronto, Toronto, Canada. [6]Department of Biotherapy and National Clinical Research Center for Geriatrics, Cancer Center, West China Hospital, Sichuan University, Chengdu, China. [7]MinSheng Ear-Nose-Throat Hospital, Chengdu, China. [8]Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu, China. [9]Department of Biostatistics, Princess Margaret Cancer Centre and Dalla Lana School of Public Health, Toronto, Canada. [10]Department of Medicine, Division of Medical Oncology and Hematology, Princess Margaret Cancer Center, University Health Network, University of Toronto, Toronto, Canada.

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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.© 2023, Cheng, Qiu, Rao et al.

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出版当年[2023]版：

大类 | 1 区

生物学

小类 | 1 区生物学

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大类 | 1 区

生物学

小类 | 1 区生物学

第一作者：

第一作者机构： [1]Department of Oto-Rhino-Laryngology, and National Clinical Research Center for Geriatrics, West China Hospital, West China Medical School, Sichuan University, Chengdu, China.

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通讯机构： [1]Department of Oto-Rhino-Laryngology, and National Clinical Research Center for Geriatrics, West China Hospital, West China Medical School, Sichuan University, Chengdu, China. [4]West China Biomedical Big Data Center, West China Hospital, Sichuan University, Chengdu, China.

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