| First Author | Chandra V | Year | 2024 |
| Journal | Cancer Cell | Volume | 42 |
| Issue | 1 | Pages | 85-100.e6 |
| PubMed ID | 38157865 | Mgi Jnum | J:352224 |
| Mgi Id | MGI:7575636 | Doi | 10.1016/j.ccell.2023.12.006 |
| Citation | Chandra V, et al. (2024) Gut epithelial Interleukin-17 receptor A signaling can modulate distant tumors growth through microbial regulation. Cancer Cell 42(1):85-100.e6 |
| abstractText | 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. |
