Tumor-resident Lactobacillus iners confer chemoradiation resistance through lactate-induced metabolic rewiring
Menée à l'aide de lignées cellulaires, d'échantillons sanguins, d'échantillons tumoraux et d'échantillons tissulaires prélevés sur des patientes atteintes d'un cancer du col utérin, cette étude met en évidence un mécanisme par lequel les bactéries Lactobacillus iners qui résident dans la tumeur confèrent aux cellules cancéreuses une chimioradiorésistance en modifiant leur métabolisme via la production d'acide lactique
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.
Cancer Cell 2023