{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T07:03:26Z","timestamp":1791270206736,"version":"4.1.0"},"reference-count":66,"publisher":"National Academy of Sciences","issue":"36","license":[{"start":{"date-parts":[[2024,8,26]],"date-time":"2024-08-26T00:00:00Z","timestamp":1724630400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"name":"Spanish Ministry of Science, Innovation and Universities","award":["RTI2018-094664-B-I00"],"award-info":[{"award-number":["RTI2018-094664-B-I00"]}]},{"name":"Spanish Ministry of Science, Innovation and Universities","award":["PID2021-122797OB-I00"],"award-info":[{"award-number":["PID2021-122797OB-I00"]}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2024,9,3]]},"abstract":"<jats:p>\n                    Lung cancer is the leading cause of cancer mortality worldwide. KRAS oncogenes are responsible for at least a quarter of lung adenocarcinomas, the main subtype of lung cancer. After four decades of intense research, selective inhibitors of KRAS oncoproteins are finally reaching the clinic. Yet, their effect on overall survival is limited due to the rapid appearance of drug resistance, a likely consequence of the high intratumoral heterogeneity characteristic of these tumors. In this study, we have attempted to identify those functional alterations that result from KRAS oncoprotein expression during the earliest stages of tumor development. Such functional changes are likely to be maintained during the entire process of tumor progression regardless of additional co-occurring mutations. Single-cell RNA sequencing analysis of murine alveolar type 2 cells expressing a resident\n                    <jats:italic>Kras<\/jats:italic>\n                    oncogene revealed impairment of the type I interferon pathway, a feature maintained throughout tumor progression. This alteration was also present in advanced murine and human tumors harboring additional mutations in the p53 or LKB1 tumor suppressors. Restoration of type I interferon (IFN) signaling by IFN-\u03b2 or constitutive active stimulator of interferon genes (STING) expression had a profound influence on the tumor microenvironment, switching them from immunologically \u201ccold\u201d to immunologically \u201chot\u201d tumors. Therefore, enhancement of the type I IFN pathway predisposes KRAS mutant lung tumors to immunotherapy treatments, regardless of co-occurring mutations in p53 or LKB1.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2402913121","type":"journal-article","created":{"date-parts":[[2024,8,26]],"date-time":"2024-08-26T15:05:06Z","timestamp":1724684706000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":21,"title":["Type I interferon signaling pathway enhances immune-checkpoint inhibition in KRAS mutant lung tumors"],"prefix":"10.1073","volume":"121","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6011-7452","authenticated-orcid":false,"given":"Fernando","family":"Fern\u00e1ndez-Garc\u00eda","sequence":"first","affiliation":[{"name":"Experimental Oncology Group, Molecular Oncology Program, Centro Nacional de Investigaciones Oncol\u00f3gicas, Madrid 28029, 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