Deciphering the interplay of HPV infection, MHC-II expression, and CXCL13+ CD4+ T cell activation in oropharyngeal cancer: implications for immunotherapy

作者：Shida Yan, Xing Zhang, Qiaohong Lin, Mingyuan Du, Yiqi Li, Shuai He, Jingtao Chen, Xiyuan Li, Jin‐Xin Bei, Shuwei Chen, Ming Song · 发表于：Cancer Immunology Immunotherapy · 年份：2024 · DOI：10.1007/s00262-024-03789-0 · 被引用次数：11 · 研究领域：Cancer Immunotherapy and Biomarkers、Head and Neck Cancer Studies、Cancer-related molecular mechanisms research

Abstract Background Human papillomavirus (HPV) infection has become an important etiological driver of oropharyngeal squamous cell carcinoma (OPSCC), leading to unique tumor characteristics. However, the interplay between HPV-associated tumor cells and tumor microenvironment (TME) remains an enigma. Methods We performed a single-cell RNA-sequencing (scRNA-seq) on HPV-positive (HPV + ) and HPV-negative (HPV ‒ ) OPSCC tumors, each for three samples, and one normal tonsil tissue. Ex vivo validation assays including immunofluorescence staining, cell line co-culture, and flow cytometry analysis were used to test specific subtypes of HPV + tumor cells and their communications with T cells. Results Through a comprehensive single-cell transcriptome analysis, we uncover the distinct transcriptional signatures between HPV + and HPV ‒ OPSCC. Specifically, HPV + OPSCC tumor cells manifest an enhanced interferon response and elevated expression of the major histocompatibility complex II (MHC-II), potentially bolstering tumor recognition and immune response. Furthermore, we identify a CXCL13 + CD4 + T cell subset that exhibits dual features of both follicular and pro-inflammatory helper T cells. Noteworthily, HPV + OPSCC tumor cells embrace extensive intercellular communications with CXCL13 + CD4 + T cells. Interaction with HPV + OPSCC tumor cells amplifies CXCL13 and IFNγ release in CD4 + T cells, fostering a pro-inflammatory TME. Additionally, HPV + tumor cells expressing high MHC-II and...