Journal
ELIFE
Volume 12, Issue -, Pages -Publisher
eLIFE SCIENCES PUBL LTD
DOI: 10.7554/eLife.82705
Keywords
tumor microenvironment; human papillomavirus; CDK4 inhibitor; proliferative exhausted CD8(+) T cells; head and neck squamous cell carcinoma; Human
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By using multi-omics sequencing, a proliferative exhausted CD8(+) T cells cluster (P-Tex) that is beneficial to the survival outcomes of patients with HPV-positive HNSCC was identified. P-Tex cells aggregate in the antigen-presenting cell niches and activate certain signaling pathways, providing modest but persistent anti-tumor effects.
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.
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