Tumor-Resident Lactobacillus iners and Chemoradiation Resistance

Mechanistic links between the cervical tumor microbiome and resistance to chemoradiation.

Overview

Clinical response to chemoradiation in cervical cancer varies widely, even among patients with similar stage and treatment. This project investigated whether tumor-resident microbiota contribute directly to treatment resistance, with a focus on Lactobacillus iners.

Working at MD Anderson Cancer Center, we combined patient-derived tumor data, microbiome profiling, and mechanistic experiments to define how specific microbial states alter therapeutic response.

Approach

  • Cervical cancer patient cohorts treated with definitive chemoradiation
  • Tumor and cervicovaginal microbiome profiling
  • Integration of microbial composition with clinical outcomes
  • In vitro and ex vivo assays to test microbial effects on treatment response
  • Metabolic and transcriptional analyses to identify resistance mechanisms

The goal was to move beyond association and establish causality.

Key Findings

  • Tumors enriched for Lactobacillus iners showed poorer response to chemoradiation
  • L. iners–derived lactate altered tumor cell metabolism and stress responses
  • Microbial metabolic byproducts directly increased resistance to DNA-damaging therapy
  • Distinct microbial states mapped to clinically meaningful outcome differences

These findings support a model where the tumor microbiome actively shapes radiation response.

Outputs

  • First-author and co-author manuscripts in preparation and submission
  • Mechanistic framework linking microbiome metabolism to radiation resistance
  • Foundation for microbiome-informed risk stratification in cervical cancer
  • Ongoing translational extensions within radiation oncology

Clinical Relevance

This work highlights the tumor microbiome as a modifier of chemoradiation response. Incorporating microbial context into treatment planning may improve risk stratification and identify patients who could benefit from microbiome-targeted interventions alongside standard radiation therapy.

Tools & Methods

Microbiome sequencing · metabolic assays · radiation response modeling · multi-omics integration · translational cancer biology