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bioRxiv · 10.1101/2022.10.27.513993

Proliferative Exhausted CD8 T Cells Exacerbate Long-lasting Anti-tumor Effects in Human Papillomavirus Positive Head and Neck Squamous Cell Carcinoma

Cheng, D.·Qiu, K.·Rao, Y.·Mao, M.·Li, L.·Wang, Y.·Song, Y.·Chen, J.·Yi, X.·Shao, X.·Huang, S. H.·Zhang, Y.·Chen, X.·Wu, S.·Yu, S.·Liu, J.·Wang, H.·Peng, X.·Li, D.·Yang, L.·Chen, L.·Ying, Z.·Zheng, Y.·Zheng, M.·Ying, B.·Zeng, X.·Xu, W.·Liu, G.·Chen, F.·Yu, H.·Zhao, Y.·Ren, J.
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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 CD8+ exhausted 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. Graphic abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=105 SRC="FIGDIR/small/513993v1_ufig1.gif" ALT="Figure 1"> View larger version (39K): org.highwire.dtl.DTLVardef@1f8810forg.highwire.dtl.DTLVardef@1e11d84org.highwire.dtl.DTLVardef@58fb6aorg.highwire.dtl.DTLVardef@1e20a13_HPS_FORMAT_FIGEXP M_FIG C_FIG

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Cheng, D., Qiu, K., Rao, Y., Mao, M., Li, L., Wang, Y., Song, Y., Chen, J., Yi, X., Shao, X., Huang, S. H., Zhang, Y., Chen, X., Wu, S., Yu, S., Liu, J., Wang, H., Peng, X., Li, D., Yang, L., Chen, L., Ying, Z., Zheng, Y., Zheng, M., Ying, B., Zeng, X., Xu, W., Liu, G., Chen, F., Yu, H., Zhao, Y., Ren, J.. 2022-10-27. Proliferative Exhausted CD8 T Cells Exacerbate Long-lasting Anti-tumor Effects in Human Papillomavirus Positive Head and Neck Squamous Cell Carcinoma. https://doi.org/10.1101/2022.10.27.513993

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