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

IF 4.6 2区 医学 Q2 IMMUNOLOGY Cancer Immunology, Immunotherapy Pub Date : 2024-08-06 DOI:10.1007/s00262-024-03789-0
Shida Yan, Xing Zhang, Qiaohong Lin, Mingyuan Du, Yiqi Li, Shuai He, Jingtao Chen, Xiyuan Li, Jinxin Bei, Shuwei Chen, Ming Song
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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 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.

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解密口咽癌中 HPV 感染、MHC-II 表达和 CXCL13+ CD4+ T 细胞活化的相互作用:对免疫疗法的影响。
背景:人乳头状瘤病毒(HPV)感染已成为口咽鳞状细胞癌(OPSCC)的重要病因,导致其具有独特的肿瘤特征。然而,HPV相关肿瘤细胞与肿瘤微环境(TME)之间的相互作用仍然是一个谜:我们对 HPV 阳性(HPV+)和 HPV 阴性(HPV-)的 OPSCC 肿瘤(各三个样本)和一个正常扁桃体组织进行了单细胞 RNA 序列分析(scRNA-seq)。体内外验证试验包括免疫荧光染色、细胞系共培养和流式细胞仪分析,用于检测HPV+肿瘤细胞的特定亚型及其与T细胞的通讯:通过全面的单细胞转录组分析,我们发现了HPV+和HPV- OPSCC之间不同的转录特征。具体来说,HPV+ OPSCC肿瘤细胞的干扰素反应增强,主要组织相容性复合体II(MHC-II)表达升高,这可能会增强肿瘤识别和免疫反应。此外,我们还发现了一种 CXCL13+CD4+ T 细胞亚群,它同时表现出滤泡和促炎辅助 T 细胞的双重特征。值得注意的是,HPV+ OPSCC 肿瘤细胞与 CXCL13+CD4+ T 细胞之间有着广泛的细胞间通讯。与 HPV+ OPSCC 肿瘤细胞的相互作用扩大了 CD4+T 细胞中 CXCL13 和 IFNγ 的释放,促进了促炎性 TME 的形成。此外,表达高MHC-II和CXCL13+CD4+T细胞的HPV+肿瘤细胞表明OPSCC患者的总生存率较高:总之,我们的研究强调了高免疫原性肿瘤细胞和 CXCL13+CD4+ T 细胞在 HPV+ OPSCC 中协调的协同炎症免疫反应,为 OPSCC 患者分层和有效免疫疗法的策略制定提供了有益的启示。
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来源期刊
CiteScore
10.50
自引率
1.70%
发文量
207
审稿时长
1 months
期刊介绍: Cancer Immunology, Immunotherapy has the basic aim of keeping readers informed of the latest research results in the fields of oncology and immunology. As knowledge expands, the scope of the journal has broadened to include more of the progress being made in the areas of biology concerned with biological response modifiers. This helps keep readers up to date on the latest advances in our understanding of tumor-host interactions. The journal publishes short editorials including "position papers," general reviews, original articles, and short communications, providing a forum for the most current experimental and clinical advances in tumor immunology.
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