Student and Faculty Publications
Publication Date
1-8-2024
Journal
Cancer Cell
Abstract
Microbes influence cancer initiation, progression and therapy responsiveness. IL-17 signaling contributes to gut barrier immunity by regulating microbes but also drives tumor growth. A knowledge gap remains regarding the influence of enteric IL-17-IL-17RA signaling and their microbial regulation on the behavior of distant tumors. We demonstrate that gut dysbiosis induced by systemic or gut epithelial deletion of IL-17RA induces growth of pancreatic and brain tumors due to excessive development of Th17, primary source of IL-17 in human and mouse pancreatic ductal adenocarcinoma, as well as B cells that circulate to distant tumors. Microbial dependent IL-17 signaling increases DUOX2 signaling in tumor cells. Inefficacy of pharmacological inhibition of IL-17RA is overcome with targeted microbial ablation that blocks the compensatory loop. These findings demonstrate the complexities of IL-17-IL-17RA signaling in different compartments and the relevance for accounting for its homeostatic host defense function during cancer therapy.
Keywords
Mice, Animals, Humans, Interleukin-17, Receptors, Interleukin-17, Mice, Knockout, Signal Transduction, Pancreatic Neoplasms
Included in
Bioinformatics Commons, Biomedical Informatics Commons, Medical Cell Biology Commons, Medical Microbiology Commons, Oncology Commons
Comments
Supplementary Materials
PMID: 38157865