Inactivation of Interferon Receptor Promotes the Establishment of Immune Privileged Tumor Microenvironment. Cancer Cell 2017 Feb 13;31(2):194-207
Date
02/16/2017Pubmed ID
28196594Pubmed Central ID
PMC5313042DOI
10.1016/j.ccell.2017.01.004Scopus ID
2-s2.0-85012931658 (requires institutional sign-in at Scopus site) 210 CitationsAbstract
Refractoriness of solid tumors, including colorectal cancers (CRCs), to immunotherapies is attributed to the immunosuppressive tumor microenvironment that protects malignant cells from cytotoxic T lymphocytes (CTLs). We found that downregulation of the type I interferon receptor chain IFNAR1 occurs in human CRC and mouse models of CRC. Downregulation of IFNAR1 in tumor stroma stimulated CRC development and growth, played a key role in formation of the immune-privileged niche, and predicted poor prognosis in human CRC patients. Genetic stabilization of IFNAR1 improved CTL survival and increased the efficacy of the chimeric antigen receptor T cell transfer and PD-1 inhibition. Likewise, pharmacologic stabilization of IFNAR1 suppressed tumor growth providing the rationale for upregulating IFNAR1 to improve anti-cancer therapies.
Author List
Katlinski KV, Gui J, Katlinskaya YV, Ortiz A, Chakraborty R, Bhattacharya S, Carbone CJ, Beiting DP, Girondo MA, Peck AR, Puré E, Chatterji P, Rustgi AK, Diehl JA, Koumenis C, Rui H, Fuchs SYMESH terms used to index this publication - Major topics in bold
AnimalsCell Survival
Colorectal Neoplasms
Down-Regulation
Humans
Immune Tolerance
Mice
Mice, Inbred C57BL
Receptor, Interferon alpha-beta
Signal Transduction
T-Lymphocytes, Cytotoxic
Tumor Microenvironment
