2. Academic Validation
  3. Sex-biased intratumoral microbiome influences tumor molecular and immune landscape and disease outcomes

Sex-biased intratumoral microbiome influences tumor molecular and immune landscape and disease outcomes

  • Cell Rep Med. 2026 May 19;7(5):102757. doi: 10.1016/j.xcrm.2026.102757.
Yuting Shan 1,  Yingbo Huang 1,  Adam Lee 1,  Radwa M Elmorsi 2,  Tuyen Phan 1,  Indrajit Chaudhury 3,  Tom Corbiere 3,  Lindsey B Collins 1,  Elizabeth B Hirsch 1,  Benjamin A Weinberg 4,  Jennifer M Johnson 5,  Emmanuel S Antonarakis 6,  Emil Lou 7,  R Stephanie Huang 8
Affiliations

Affiliations

  • 1 Department of Experimental and Clinical Pharmacology, College of Pharmacy, University of Minnesota, Minneapolis, MN, USA.
  • 2 Department of Experimental and Clinical Pharmacology, College of Pharmacy, University of Minnesota, Minneapolis, MN, USA; Department of Pharmacology, Faculty of Medicine, Tanta University, Tanta, Egypt.
  • 3 Caris Life Sciences, Irving, TX, USA.
  • 4 Ruesch Center for the Cure of Gastrointestinal Cancers, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC, USA.
  • 5 Department of Otolaryngology - Head and Neck Surgery, Thomas Jefferson University Hospital, Philadelphia, PA, USA.
  • 6 Masonic Cancer Center, University of Minnesota, Minneapolis, MN, USA.
  • 7 Masonic Cancer Center, University of Minnesota, Minneapolis, MN, USA; Division of Hematology, Oncology and Transplantation, University of Minnesota, Minneapolis, MN, USA.
  • 8 Department of Experimental and Clinical Pharmacology, College of Pharmacy, University of Minnesota, Minneapolis, MN, USA; Masonic Cancer Center, University of Minnesota, Minneapolis, MN, USA. Electronic address: [email protected].
PMID: 42013847 DOI: 10.1016/j.xcrm.2026.102757
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.

Keywords

aerodigestive and gastrointestinal cancers; chemotherapy response; intratumoral microbiome; overall survival; sex differences; tumor genomics.

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