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

Autor: Yan S; Department of Head and Neck Surgery, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, 651 Dongfeng Road East, Guangzhou, 510060, China.; State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, 510060, China., Zhang X; Department of Head and Neck Surgery, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, 651 Dongfeng Road East, Guangzhou, 510060, China.; State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, 510060, China., Lin Q; Department of Head and Neck Surgery, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, 651 Dongfeng Road East, Guangzhou, 510060, China.; State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, 510060, China., Du M; Department of Head and Neck Surgery, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, 651 Dongfeng Road East, Guangzhou, 510060, China.; State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, 510060, China., Li Y; State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, 510060, China., He S; State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, 510060, China., Chen J; Department of Head and Neck Surgery, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, 651 Dongfeng Road East, Guangzhou, 510060, China.; State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, 510060, China., Li X; Department of Head and Neck Surgery, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, 651 Dongfeng Road East, Guangzhou, 510060, China.; State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, 510060, China., Bei J; State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, 510060, China., Chen S; Department of Head and Neck Surgery, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, 651 Dongfeng Road East, Guangzhou, 510060, China. chenshuw@sysucc.org.cn.; State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, 510060, China. chenshuw@sysucc.org.cn., Song M; Department of Head and Neck Surgery, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, 651 Dongfeng Road East, Guangzhou, 510060, China. songming@sysucc.org.cn.; State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, 510060, China. songming@sysucc.org.cn.
Jazyk: angličtina
Zdroj: Cancer immunology, immunotherapy : CII [Cancer Immunol Immunother] 2024 Aug 06; Vol. 73 (10), pp. 206. Date of Electronic Publication: 2024 Aug 06.
DOI: 10.1007/s00262-024-03789-0
Abstrakt: 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 CXCL13 + CD4 + T cell prevalence are indicative of favorable overall survival rates in OPSCC patients.
Conclusions: Together, our study underscores a synergistic inflammatory immune response orchestrated by highly immunogenic tumor cells and CXCL13 + CD4 + T cells in HPV + OPSCC, offering useful insights into strategy development for patient stratification and effective immunotherapy in OPSCC.
(© 2024. The Author(s).)
Databáze: MEDLINE
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