Dataset Information

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

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.

SUBMITTER: Yan S

PROVIDER: S-EPMC11303625 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature

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Publications

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

Yan Shida S Zhang Xing X Lin Qiaohong Q Du Mingyuan M Li Yiqi Y He Shuai S Chen Jingtao J Li Xiyuan X Bei Jinxin J Chen Shuwei S Song Ming M

Cancer immunology, immunotherapy : CII 20240806 10

<h4>Background</h4>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.<h4>Methods</h4>We performed a single-cell RNA-sequencing (scRNA-seq) on HPV-positive (HPV<sup>+</sup>) and HPV-negative (HPV<sup>‒</sup>) OPSCC tumors, each for three samples, and one normal tonsil ti ...[more]

PMID: 39105803

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Project description:BackgroundDysbiotic vaginal microbiota have been implicated as contributors to persistent HPV-mediated cervical carcinogenesis and genital inflammation with mechanisms unknown. Given that cancer is a metabolic disease, metabolic profiling of the cervicovaginal microenvironment has the potential to reveal the functional interplay between the host and microbes in HPV persistence and progression to cancer.MethodsOur study design included HPV-negative/positive controls, women with low-grade and high-grade cervical dysplasia, or cervical cancer (n = 78). Metabolic fingerprints were profiled using liquid chromatography-mass spectrometry. Vaginal microbiota and genital inflammation were analysed using 16S rRNA gene sequencing and immunoassays, respectively. We used an integrative bioinformatic pipeline to reveal host and microbe contributions to the metabolome and to comprehensively assess the link between HPV, microbiota, inflammation and cervical disease.FindingsMetabolic analysis yielded 475 metabolites with known identities. Unique metabolic fingerprints discriminated patient groups from healthy controls. Three-hydroxybutyrate, eicosenoate, and oleate/vaccenate discriminated (with excellent capacity) between cancer patients versus the healthy participants. Sphingolipids, plasmalogens, and linoleate positively correlated with genital inflammation. Non-Lactobacillus dominant communities, particularly in high-grade dysplasia, perturbed amino acid and nucleotide metabolisms. Adenosine and cytosine correlated positively with Lactobacillus abundance and negatively with genital inflammation. Glycochenodeoxycholate and carnitine metabolisms connected non-Lactobacillus dominance to genital inflammation.InterpretationCervicovaginal metabolic profiles were driven by cancer followed by genital inflammation, HPV infection, and vaginal microbiota. This study provides evidence for metabolite-driven complex host-microbe interactions as hallmarks of cervical cancer with future translational potential. FUND: Flinn Foundation (#1974), Banner Foundation Obstetrics/Gynecology, and NIH NCI (P30-CA023074).

Dataset Information

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

Background

Methods

Results

Conclusions

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Dataset Information

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

Background

Methods

Results

Conclusions

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

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