Tumor-resident Lactobacillus iners confer chemoradiation resistance through lactate-induced metabolic rewiring

Authors

Lauren E. Colbert, The University of Texas MD Anderson Cancer Center
Molly B. El Alam, The University of Texas MD Anderson Cancer Center
Rui Wang, The University of Texas MD Anderson Cancer Center
Tatiana Karpinets, The University of Texas MD Anderson Cancer Center
David Lo, The University of Texas MD Anderson Cancer Center
Erica J. Lynn, The University of Texas MD Anderson Cancer Center
Timothy A. Harris, The University of Texas MD Anderson Cancer Center
Jacob H. Elnaggar, LSU Health Sciences Center - New OrleansFollow
Kyoko Yoshida-Court, The University of Texas MD Anderson Cancer Center
Katarina Tomasic, The University of Texas MD Anderson Cancer Center
Julianna K. Bronk, The University of Texas MD Anderson Cancer Center
Julie Sammouri, The University of Texas MD Anderson Cancer Center
Ananta V. Yanamandra, The University of Texas MD Anderson Cancer Center
Adilene V. Olvera, The University of Texas MD Anderson Cancer Center
Lily G. Carlin, The University of Texas MD Anderson Cancer Center
Travis Sims, The University of Texas MD Anderson Cancer Center
Andrea Y. Delgado Medrano, The University of Texas MD Anderson Cancer Center
Tatiana Cisneros Napravnik, The University of Texas MD Anderson Cancer Center
Madison O'Hara, The University of Texas MD Anderson Cancer Center
Daniel Lin, The University of Texas MD Anderson Cancer Center
Chike O. Abana, The University of Texas MD Anderson Cancer Center
Hannah X. Li, The University of Texas MD Anderson Cancer Center
Patricia J. Eifel, The University of Texas MD Anderson Cancer Center
Anuja Jhingran, The University of Texas MD Anderson Cancer Center
Melissa Joyner, The University of Texas MD Anderson Cancer Center
Lilie Lin, The University of Texas MD Anderson Cancer Center
Lois M. Ramondetta, The University of Texas MD Anderson Cancer Center
Andrew M. Futreal, The University of Texas MD Anderson Cancer Center

Document Type

Article

Publication Date

10-19-2023

Publication Title

Cancer Cell

Abstract

Tumor microbiota can produce active metabolites that affect cancer and immune cell signaling, metabolism, and proliferation. Here, we explore tumor and gut microbiome features that affect chemoradiation response in patients with cervical cancer using a combined approach of deep microbiome sequencing, targeted bacterial culture, and in vitro assays. We identify that an obligate L-lactate-producing lactic acid bacterium found in tumors, Lactobacillus iners, is associated with decreased survival in patients, induces chemotherapy and radiation resistance in cervical cancer cells, and leads to metabolic rewiring, or alterations in multiple metabolic pathways, in tumors. Genomically similar L-lactate-producing lactic acid bacteria commensal to other body sites are also significantly associated with survival in colorectal, lung, head and neck, and skin cancers. Our findings demonstrate that lactic acid bacteria in the tumor microenvironment can alter tumor metabolism and lactate signaling pathways, causing therapeutic resistance. Lactic acid bacteria could be promising therapeutic targets across cancer types.

First Page

1945

Last Page

1962.e11

PubMed ID

37863066

Volume

41

Issue

11

Creative Commons License

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

Recommended Citation

Colbert, Lauren E.; El Alam, Molly B.; Wang, Rui; Karpinets, Tatiana; Lo, David; Lynn, Erica J.; Harris, Timothy A.; Elnaggar, Jacob H.; Yoshida-Court, Kyoko; Tomasic, Katarina; Bronk, Julianna K.; Sammouri, Julie; Yanamandra, Ananta V.; Olvera, Adilene V.; Carlin, Lily G.; Sims, Travis; Delgado Medrano, Andrea Y.; Napravnik, Tatiana Cisneros; O'Hara, Madison; Lin, Daniel; Abana, Chike O.; Li, Hannah X.; Eifel, Patricia J.; Jhingran, Anuja; Joyner, Melissa; Lin, Lilie; Ramondetta, Lois M.; and Futreal, Andrew M., "Tumor-resident Lactobacillus iners confer chemoradiation resistance through lactate-induced metabolic rewiring" (2023). School of Medicine Faculty Publications. 1615.
https://digitalscholar.lsuhsc.edu/som_facpubs/1615
10.1016/j.ccell.2023.09.012