Gut microbiome diversity is an independent predictor of survival in cervical cancer patients receiving chemoradiation

• Published in: Communications biology Vol. 4; no. 1; pp. 237 - 10
• Main Authors: Sims, Travis T., El Alam, Molly B., Karpinets, Tatiana V., Dorta-Estremera, Stephanie, Hegde, Venkatesh L., Nookala, Sita, Yoshida-Court, Kyoko, Wu, Xiaogang, Biegert, Greyson W. G., Delgado Medrano, Andrea Y., Solley, Travis, Ahmed-Kaddar, Mustapha, Chapman, Bhavana V., Sastry, K. Jagannadha, Mezzari, Melissa P., Petrosino, Joseph F., Lin, Lilie L., Ramondetta, Lois, Jhingran, Anuja, Schmeler, Kathleen M., Ajami, Nadim J., Wargo, Jennifer, Colbert, Lauren E., Klopp, Ann H.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 22.02.2021; Nature Publishing Group; Nature Portfolio
• Subjects: 45; 45/91; 631/67/1517/1371; 692/4028/67/1517/1371; Adult; Aged; Antigens, CD - metabolism; Antigens, Differentiation, T-Lymphocyte - metabolism; Biology; Biomedical and Life Sciences; Cancer therapies; CD4 antigen; CD4-Positive T-Lymphocytes - immunology; CD4-Positive T-Lymphocytes - metabolism; CD69 antigen; Cervical cancer; Cervix; Chemoradiotherapy; Chemoradiotherapy - adverse effects; Chemoradiotherapy - mortality; Female; Flow cytometry; Gastrointestinal Microbiome; Humans; Immunotherapy; Infiltration; Intestinal microflora; Intestines - microbiology; Ki-67 Antigen - metabolism; Lectins, C-Type - metabolism; Life Sciences; Lymphocytes; Lymphocytes, Tumor-Infiltrating - immunology; Lymphocytes, Tumor-Infiltrating - metabolism; Metastases; Microbiomes; Microbiota; Middle Aged; Prospective Studies; Radiation therapy; Risk factors; Time Factors; Treatment Outcome; Tumor Microenvironment; Uterine Cervical Neoplasms - immunology; Uterine Cervical Neoplasms - microbiology; Uterine Cervical Neoplasms - mortality; Uterine Cervical Neoplasms - therapy
• ISSN: 2399-3642; 2399-3642
• DOI: 10.1038/s42003-021-01741-x

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. Travis Sims and Molly El Alam et al. show that diversity of gut microbiota is associated with a favorable response to chemoradiation for cervical cancer and use flow cytometry to show that patients with high microbiome diversity had increased tumor infiltration of CD4+ lymphocytes as well as activated subsets of CD4 cells expressing ki67+ and CD69+ throughout radiation therapy. These results reveal how modulation of the gut microbiota could potentially be used to improve treatment efficacy and outcome.