Sex-biased intratumoral microbiome influences tumor molecular and immune landscape and disease outcomes.
basic_science · Level V
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- Record sourced from PubMed, PMID 42013847.
- Also identified by DOI 10.1016/j.xcrm.2026.102757.
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Abstract
The intratumoral microbiome is increasingly recognized as a regulator of cancer biology, yet sex-specific patterns and their relevance to cancer disparities remain poorly understood. We perform a multi-kingdom analysis of more than 5,000 tumors from seven datasets to identify sex-differential microbial taxa across aerodigestive and gastrointestinal cancers. We identify and validate 22 taxa with consistent sex-biased abundance, including in real-world cohort. These microbes show cancer-type- and microbe-specific associations with tumor transcriptomes, oncogenic pathways, and immune cell infiltration. Female-enriched microbes are linked to increased estrogen signaling and interferon responses, whereas male-enriched taxa show opposing patterns. In gastric cancer, intratumoral Epstein-Barr virus is enriched in males and associated with higher CD8<sup>+</sup> T cell infiltration and improved survival. Functional co-culture experiments demonstrate that sex-biased microbes modulate chemotherapy sensitivity. Together, these findings reveal a sex-biased intratumoral microbiome axis that shapes tumor phenotypes and disease outcomes, highlighting opportunities for microbiota-guided, sex-aware approaches in oncology.