Tumor-Induced IL-6 Reprograms Host Metabolism to Suppress Anti-tumor Immunity

• DOI: 10.1016/j.cmet.2016.10.010
• Publication Date: 2016-11-08T17:00:31Z
• Authors: Thomas R. Flint; Tobias Janowitz; Claire M. Connell; Edward W. Roberts; Alice E. Denton; Anthony P. Coll; Duncan I. Jodrell; Douglas T. Fearon
• Keywords: Corticosterone; Ketogenesis; Immunosurveillance; Ketogenic Diet

In patients with cancer, the wasting syndrome, cachexia, is associated caloric deficiency. Here, we describe tumor-induced alterations of host metabolic response to deficiency that cause intratumoral immune suppression. pre-cachectic mice transplanted colorectal cancer or autochthonous pancreatic ductal adenocarcinoma (PDA), find IL-6 reduces hepatic ketogenic potential through suppression PPARalpha, transcriptional master regulator ketogenesis. When these are challenged deficiency, resulting relative hypoketonemia triggers a marked rise in glucocorticoid levels. Multiple pathways suppressed by this hormonal stress response. Moreover, administering corticosterone elevate plasma level lower than occurring cachectic abolishes mouse PDA an immunotherapy has advanced clinical trials. Therefore, impairs reduced intake, systemic blocks anti-cancer immunotherapy.