| Literature DB >> 28196594 |
Kanstantsin V Katlinski1, Jun Gui1, Yuliya V Katlinskaya1, Angelíca Ortiz1, Riddhita Chakraborty1, Sabyasachi Bhattacharya1, Christopher J Carbone1, Daniel P Beiting2, Melanie A Girondo3, Amy R Peck3, Ellen Puré1, Priya Chatterji4, Anil K Rustgi4, J Alan Diehl5, Constantinos Koumenis6, Hallgeir Rui3, Serge Y Fuchs7.
Abstract
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.Entities:
Keywords: IFNAR1; colorectal cancer; cytotoxic T cells; immunosuppression; interferon; receptor; tumor microenvironment
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Year: 2017 PMID： 28196594 PMCID： PMC5313042 DOI： 10.1016/j.ccell.2017.01.004
Source DB: PubMed Journal: Cancer Cell ISSN： 1535-6108 Impact factor: 31.743