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Alliance"],"published-print":{"date-parts":[[2019,6]]},"abstract":"<jats:p>\n                    Targeting PD-1\/PD-L1 is only effective in \u223c20% of lung cancer patients, but determinants of this response are poorly defined. We previously observed differential responses of two murine K-Ras\u2013mutant lung cancer cell lines to anti\u2013PD-1 therapy: CMT167 tumors were eliminated, whereas Lewis Lung Carcinoma (LLC) tumors were resistant. The goal of this study was to define mechanism(s) mediating this difference. RNA sequencing analysis of cancer cells recovered from lung tumors revealed that CMT167 cells induced an IFN\u03b3 signature that was blunted in LLC cells. Silencing\n                    <jats:italic>Ifngr1<\/jats:italic>\n                    in CMT167 resulted in tumors resistant to IFN\u03b3 and anti\u2013PD-1 therapy. Conversely, LLC cells had high basal expression of SOCS1, an inhibitor of IFN\u03b3. Silencing\n                    <jats:italic>Socs1<\/jats:italic>\n                    increased response to IFN\u03b3 in vitro and sensitized tumors to anti\u2013PD-1. This was associated with a reshaped tumor microenvironment, characterized by enhanced T cell infiltration and enrichment of PD-L1\n                    <jats:sup>hi<\/jats:sup>\n                    myeloid cells. These studies demonstrate that targeted enhancement of tumor-intrinsic IFN\u03b3 signaling can induce a cascade of changes associated with increased therapeutic vulnerability.\n                  <\/jats:p>","DOI":"10.26508\/lsa.201900328","type":"journal-article","created":{"date-parts":[[2019,5,27]],"date-time":"2019-05-27T14:45:13Z","timestamp":1558968313000},"page":"e201900328","update-policy":"https:\/\/doi.org\/10.26508\/lsa.crossmarkpolicy","source":"Crossref","is-referenced-by-count":45,"title":["Tumor-intrinsic response to IFN\u03b3 shapes the tumor microenvironment and anti\u2013PD-1 response in NSCLC"],"prefix":"10.26508","volume":"2","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1580-0292","authenticated-orcid":true,"given":"Bonnie L","family":"Bullock","sequence":"first","affiliation":[{"name":"Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, 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