Intratumoral <i>Parvimonas micra</i> promotes esophageal squamous cell carcinoma via <i>p</i>-cresol-induced T_reg differentiation.

Abstract

Intratumoral microbiota has emerged as a notable factor influencing cancer initiation and progression. However, its composition and functional impact in esophageal squamous cell carcinoma (ESCC) remain largely unexplored. Here, we performed metagenomic sequencing on 119 paired tumor-normal tissues from patients with ESCC and single-cell RNA sequencing on 45 samples to investigate microbe-host interactions. We identified <i>Parvimonas micra</i> (<i>P. micra</i>), an anaerobic oral-derived bacterium, as significantly enriched in tumor tissues and associated with poor prognosis. Moreover, the abundance of <i>P. micra</i> correlated with increased regulatory T cell (T_reg cell) infiltration in the ESCC tumor microenvironment. Through cellular and animal experiments, we demonstrate that <i>P. micra</i> promotes tumor growth by secreting <i>p</i>-cresol, a metabolite of amino acid fermentation, which elevates reactive oxygen species levels and induces FOXP3⁺ T_reg differentiation, thereby fostering immunosuppression and tumor growth. Our study establishes a mechanistic link between intratumoral microbiota and the immune microenvironment, highlighting the microbial contribution to ESCC progression and prognosis.