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ORIGINAL RESEARCH article

Front. Oncol.

Sec. Head and Neck Cancer

Volume 15 - 2025 | doi: 10.3389/fonc.2025.1616928

Intratumoral microbial abundance and load influence the immune microenvironment of oral squamous cell carcinoma

Provisionally accepted
Jiajun  FangJiajun Fang1,2Mengna  WuMengna Wu1,2Hongyu  ShenHongyu Shen1,2Weijie  LiuWeijie Liu1,2Tonghan  ZhangTonghan Zhang1,2*
  • 1Hospital of Stomatology, Zhongshan City, Zhongshan, China
  • 2School of Stomatology, Jinan University, Guangzhou, Guangdong Province, China

The final, formatted version of the article will be published soon.

ObjectiveThis study aimed to explore the characteristics intratumoral microbiome in oral squamous cell carcinoma, and elucidate the interplay between intratumoral microbial profiles (relative abundance/absolute load) and tumor-infiltrating lymphocytes markers (CD4+/CD8+/FOXP3) and PD-L1 in oral squamous cell carcinomaMethodsWe analyzed 45 OSCC tissue samples alongside paired paracancerous (n=10) and normal oral microbiota controls (n=8). Microbial composition was characterized by 16S rRNA sequencing (V3-V4 regions), with bacterial load quantified via qPCR targeting the V4-1 region. Tumor-infiltrating lymphocytes markers were assessed by immunohistochemistry.ResultsSpirochaetota was concentrated in the CD4+ as well as CD8+ low infiltration groups, Proteobacteria in the CD8+ high infiltration group and Actinobacteriota in the FOXP3 low infiltration group. Tumor microbial load was negatively correlated with CD4+, CD8+, and FOXP3, but of these, only the correlation coefficient of -0.309 for CD4+ was statistically significant. However, no significant correlation was observed in the analysis of PD-L1 expression with the relative abundance of intratumoral microbiome, α-diversity, and intratumoral microbial load valuesConclusionChanges in the abundance of specific intratumoral microbiome affect the infiltration of TILs markers, and there is a negative relationship between intratumoral microbial load and T-cell infiltration, suggesting that intratumoral microbiome contribute to the processes of the tumor immunosuppressive microenvironment.

Keywords: oral squamous cell carcinoma, Intratumoral microbiome, Tumorinfiltrating lymphocytes, immune checkpoints, Immunotherapy

Received: 23 Apr 2025; Accepted: 29 Jul 2025.

Copyright: © 2025 Fang, Wu, Shen, Liu and Zhang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Tonghan Zhang, Hospital of Stomatology, Zhongshan City, Zhongshan, 528400, China

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