Department of Oto-Rhino-Laryngology, and National Clinical Research Center for Geriatrics, West China Hospital, West China Medical School, Sichuan University, Chengdu, China.
Institute of Clinical Pathology, West China Hospital, Sichuan University, Chengdu, China.
Elife. 2023 Feb 22;12:e82705. doi: 10.7554/eLife.82705.
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.
人乳头瘤病毒（HPV）阳性和 HPV 阴性头颈部鳞状细胞癌（HNSCC）的生存预后有很大的不同，对于 HNSCC 中浸润性耗竭 CD8 T 细胞（Tex）的抗肿瘤机制知之甚少。我们对人类 HNSCC 样本进行了细胞水平的多组学测序，以破译 Tex 细胞的多维特征。鉴定出一个有利于 HPV 阳性 HNSCC 患者生存结果的增殖性耗竭 CD8 T 细胞簇（P-Tex）。有趣的是，P-Tex 细胞表达的 CDK4 基因与癌细胞一样高，CDK4 抑制剂可同时抑制这些基因，这可能是 CDK4 抑制剂治疗 HPV 阳性 HNSCC 无效的潜在原因。P-Tex 细胞可以聚集在抗原呈递细胞龛中并激活某些信号通路。总之，我们的研究结果表明，P-Tex 细胞通过提供适度但持续的抗肿瘤作用，在 HPV 阳性 HNSCC 患者的预后中可能发挥重要作用。
