Esophageal squamous cell carcinoma (ESCC) remains one of the most prevalent and challenging malignancies globally, with nearly half of all cases occurring in China. Although immune checkpoint blockade has redefined the treatment landscape for ESCC, durable clinical benefits are frequently hampered by the intricate cellular and molecular heterogeneity within the tumor immune microenvironment. While the crosstalk between the intratumoral microbiome and immunity is increasingly recognized, a systematic understanding of the microbial landscape in ESCC progression has remained elusive.

To address this knowledge gap, a study led by Profs. LI Mingkun and ZHANG Li from the China National Center for Bioinformation, a research center affiliated to the Chinese Academy of Sciences, in collaboration with researchers from the Cancer Hospital of the Chinese Academy of Medical Sciences (CAMS), has characterized a novel bacteria–metabolite–immune axis that drives ESCC progression.

The findings were published in Science Advances on February 20.

Through metagenomic profiling of 119 paired tumor and adjacent normal tissues, the researchers identified a significant enrichment of Parvimonas micra (P. micra)—an anaerobic, oral-derived bacterium—in tumor tissues, which was associated with poor prognosis in ESCC patients.

Further single-cell transcriptomic analyses and histological staining revealed a positive correlation between P. micra abundance and the infiltration of regulatory T cells (T_reg cell) within the tumor microenvironment.

Mechanistically, the study demonstrates that P. micra promotes tumor progression by secreting p-cresol, a tyrosine-derived metabolite. This metabolite elevates reactive oxygen species levels and induces FOXP3⁺ T_reg differentiation, thereby fostering immunosuppression and facilitating tumor growth.

These findings establish a mechanistic link between the intratumoral microbiota and the tumor immune microenvironment, highlighting the critical role of microbes in ESCC progression and patient prognosis.