The Pancreatic Cancer Microbiome Promotes Oncogenesis by Induction of Innate and Adaptive Immune Suppression

摘要: We found that the cancerous pancreas harbors a markedly more abundant microbiome compared with normal in both mice and humans, select bacteria are differentially increased tumorous gut. Ablation of protects against preinvasive invasive pancreatic ductal adenocarcinoma (PDA), whereas transfer from PDA-bearing hosts, but not controls, reverses tumor protection. Bacterial ablation was associated immunogenic reprogramming PDA microenvironment, including reduction myeloid-derived suppressor cells an increase M1 macrophage differentiation, promoting TH1 differentiation CD4+ T CD8+ T-cell activation. also enabled efficacy for checkpoint-targeted immunotherapy by upregulating PD-1 expression. Mechanistically, generated tolerogenic immune program activating Toll-like receptors monocytic cells. These data suggest endogenous microbiota promote crippling immune-suppression characteristic has potential as therapeutic target modulation disease progression.Significance: distinct drives suppressive cellular cancer via selective receptor ligation leading to anergy. Targeting oncogenesis, intratumoral tolerance, enables checkpoint-based immunotherapy. have implications understanding suppression its reversal clinic. Cancer Discov; 8(4); 403-16. ©2018 AACR.See related commentary Riquelme et al., p. 386This article is highlighted In This Issue feature, 371.