1. Gut microbiome diversity is an independent predictor of survival in cervical cancer patients receiving chemoradiation.
- Author
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Sims TT, El Alam MB, Karpinets TV, Dorta-Estremera S, Hegde VL, Nookala S, Yoshida-Court K, Wu X, Biegert GWG, Delgado Medrano AY, Solley T, Ahmed-Kaddar M, Chapman BV, Sastry KJ, Mezzari MP, Petrosino JF, Lin LL, Ramondetta L, Jhingran A, Schmeler KM, Ajami NJ, Wargo J, Colbert LE, and Klopp AH
- Subjects
- Adult, Aged, Antigens, CD metabolism, Antigens, Differentiation, T-Lymphocyte metabolism, CD4-Positive T-Lymphocytes immunology, CD4-Positive T-Lymphocytes metabolism, Female, Humans, Ki-67 Antigen metabolism, Lectins, C-Type metabolism, Lymphocytes, Tumor-Infiltrating immunology, Lymphocytes, Tumor-Infiltrating metabolism, Middle Aged, Prospective Studies, Time Factors, Treatment Outcome, Tumor Microenvironment, Uterine Cervical Neoplasms immunology, Uterine Cervical Neoplasms microbiology, Uterine Cervical Neoplasms mortality, Chemoradiotherapy adverse effects, Chemoradiotherapy mortality, Gastrointestinal Microbiome, Intestines microbiology, Uterine Cervical Neoplasms therapy
- Abstract
Diversity of the gut microbiome is associated with higher response rates for cancer patients receiving immunotherapy but has not been investigated in patients receiving radiation therapy. Additionally, current studies investigating the gut microbiome and outcomes in cancer patients may not have adjusted for established risk factors. Here, we sought to determine if diversity and composition of the gut microbiome was independently associated with survival in cervical cancer patients receiving chemoradiation. Our study demonstrates that the diversity of gut microbiota is associated with a favorable response to chemoradiation. Additionally, compositional variation among patients correlated with short term and long-term survival. Short term survivor fecal samples were significantly enriched in Porphyromonas, Porphyromonadaceae, and Dialister, whereas long term survivor samples were significantly enriched in Escherichia Shigella, Enterobacteriaceae, and Enterobacteriales. Moreover, analysis of immune cells from cervical tumor brush samples by flow cytometry revealed that patients with a high microbiome diversity had increased tumor infiltration of CD4+ lymphocytes as well as activated subsets of CD4 cells expressing ki67+ and CD69+ over the course of radiation therapy. Modulation of the gut microbiota before chemoradiation might provide an alternative way to enhance treatment efficacy and improve treatment outcomes in cervical cancer patients.
- Published
- 2021
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