Sex-Biased Intratumoral Microbiome Influences Tumor Molecular and Immune Landscape and Disease Outcomes

Authors

• Yuting Shan
• Yingbo Huang
• Adam Lee
• Radwa M. Elmorsi
• Tuyen Phan
• Indrajit Chaudhury
• Tom Corbiere
• Lindsey B. Collins
• Elizabeth B. Hirsch
• Benjamin A. Weinberg
• Jennifer M. Johnson, Thomas Jefferson UniversityFollow
• Emmanuel S. Antonarakis
• Emil Lou
• R. Stephanie Huang

Document Type

Article

Publication Date

5-19-2026

Comments

This article is the author’s final published version in Cell Reports Medicine, Volume 7, Issue 5, 2026, Article number 102757.

The published version is available at https://doi.org/10.1016/j.xcrm.2026.102757. Copyright © 2026 The Authors.

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⁺ 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.

Recommended Citation

Shan, Yuting; Huang, Yingbo; Lee, Adam; Elmorsi, Radwa M.; Phan, Tuyen; Chaudhury, Indrajit; Corbiere, Tom; Collins, Lindsey B.; Hirsch, Elizabeth B.; Weinberg, Benjamin A.; Johnson, Jennifer M.; Antonarakis, Emmanuel S.; Lou, Emil; and Huang, R. Stephanie, "Sex-Biased Intratumoral Microbiome Influences Tumor Molecular and Immune Landscape and Disease Outcomes" (2026). Department of Otolaryngology - Head and Neck Surgery Faculty Papers. Paper 114.
https://jdc.jefferson.edu/otofp/114

Creative Commons License

This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.

PubMed ID

42013847

Language

English