Inactivation of interferon signaling promotes the establishment of an immunosuppressive microenvironment in colorectal cancers

ABSTRACT: Tumors arise and grow despite anti-cancer immune responses. These responses can be stimulated by immunotherapies such as immune checkpoint inhibitors (e.g. anti-PD1 antibodies) and chimeric antigen receptors (CAR). Efficacy of these agents in solid tumors including colorectal cancers (CRC) is limited by immunosuppressive tumor microenvironment (TME) that prevents killing of malignant cells by cytotoxic T lymphocytes (CTL). Understanding the nature of TME-generated immunosuppression is of paramount importance. Here we report that TME elicited immunosuppression via eliminating activated CTL; this elimination required TME stress-induced downregulation of the IFNAR1 chain of type I interferon (IFN) receptor and attenuation of its signaling. Downregulation of IFNAR1 was observed in human colore

ORGANISM(S): Mus musculus

SUBMITTER: daniel beiting 

PROVIDER: E-GEOD-76889 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress