[PDF][PDF] Inactivation of interferon receptor promotes the establishment of immune privileged tumor microenvironment

KV Katlinski, J Gui, YV Katlinskaya, A Ortiz… - Cancer cell, 2017 - cell.com
KV Katlinski, J Gui, YV Katlinskaya, A Ortiz, R Chakraborty, S Bhattacharya, CJ Carbone…
Cancer cell, 2017cell.com
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 …
Summary
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.
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