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Publication : Proteobacteria impair anti-tumor immunity in the omentum by consuming arginine.

First Author  Meza-Perez S Year  2024
Journal  Cell Host Microbe Volume  32
Issue  7 Pages  1177-1191.e7
PubMed ID  38942027 Mgi Jnum  J:360196
Mgi Id  MGI:7665142 Doi  10.1016/j.chom.2024.06.003
Citation  Meza-Perez S, et al. (2024) Proteobacteria impair anti-tumor immunity in the omentum by consuming arginine. Cell Host Microbe 32(7):1177-1191.e7
abstractText  Gut microbiota influence anti-tumor immunity, often by producing immune-modulating metabolites. However, microbes consume a variety of metabolites that may also impact host immune responses. We show that tumors grow unchecked in the omenta of microbe-replete mice due to immunosuppressive Tregs. By contrast, omental tumors in germ-free, neomycin-treated mice or mice colonized with altered Schaedler's flora (ASF) are spontaneously eliminated by CD8(+) T cells. These mice lack Proteobacteria capable of arginine catabolism, causing increases in serum arginine that activate the mammalian target of the rapamycin (mTOR) pathway in Tregs to reduce their suppressive capacity. Transfer of the Proteobacteria, Escherichia coli (E. coli), but not a mutant unable to catabolize arginine, to ASF mice reduces arginine levels, restores Treg suppression, and prevents tumor clearance. Supplementary arginine similarly decreases Treg suppressive capacity, increases CD8(+) T cell effectiveness, and reduces tumor burden. Thus, microbial consumption of arginine alters anti-tumor immunity, offering potential therapeutic strategies for tumors in visceral adipose tissue.
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