{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,24]],"date-time":"2025-10-24T08:18:10Z","timestamp":1761293890478,"version":"3.40.5"},"reference-count":43,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2019,3,4]],"date-time":"2019-03-04T00:00:00Z","timestamp":1551657600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P50 CA097190\u201013","R01 CA206517\u201002 (RLF)"],"award-info":[{"award-number":["P50 CA097190\u201013","R01 CA206517\u201002 (RLF)"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Head &amp; Neck"],"published-print":{"date-parts":[[2019,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Mechanisms of resistance to immune\u2010modulating cancer treatments are poorly understood. Using a novel cohort of patients with head and neck squamous cell carcinoma (HNSCC), we investigated mechanisms of immune escape from epidermal growth factor receptor\u2010specific monoclonal antibody (mAb) therapy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>HNSCC tumors (n\u2009=\u200920) from a prospective trial of neoadjuvant cetuximab monotherapy underwent whole\u2010exome sequencing. Expression of killer\u2010cell immunoglobulin\u2010like receptor (KIR) and human leukocyte antigen\u2010C (HLA\u2010C) and the effect of KIR blockade were assessed in HNSCC cell lines.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Nonresponders to cetuximab had an increased rate of mutations in HLA\u2010C compared to responders and HNSCC tumors (n\u2009=\u2009528) in The Cancer Genome Atlas (<jats:italic>P<\/jats:italic>\u2009&lt;\u20090.00001). In vitro, cetuximab\u2010activated natural killer (NK) cells induced upregulation of HLA\u2010C on HNSCC cells (<jats:italic>P<\/jats:italic>\u2009&lt;\u20090.01) via interferon gamma. Treatment of NK cells with the anti\u2010KIR mAb lirilumab increased killing of HNSCC cells (<jats:italic>P<\/jats:italic>\u2009&lt;\u20090.001).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Alterations in HLA\u2010C may provide a mechanism of immune evasion through disruption of NK activation.<\/jats:p><\/jats:sec>","DOI":"10.1002\/hed.25726","type":"journal-article","created":{"date-parts":[[2019,3,4]],"date-time":"2019-03-04T09:36:50Z","timestamp":1551692210000},"page":"2591-2601","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Immunogenomic correlates of response to cetuximab monotherapy in head and neck squamous cell carcinoma"],"prefix":"10.1002","volume":"41","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5284-7762","authenticated-orcid":false,"given":"Daniel L.","family":"Faden","sequence":"first","affiliation":[{"name":"Department of Otolaryngology, Division of Head and Neck Surgical Oncology Massachusetts Eye and Ear Infirmary  Boston Massachusetts"},{"name":"Harvard Medical School  Boston Massachusetts"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fernando","family":"Concha\u2010Benavente","sequence":"additional","affiliation":[{"name":"Department of Immunology University of Pittsburgh  Pittsburgh Pennsylvania"},{"name":"University of Pittsburgh Cancer Institute  Pittsburgh Pennsylvania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anish B.","family":"Chakka","sequence":"additional","affiliation":[{"name":"Department of Biomedical Informatics University of Pittsburgh  Pittsburgh Pennsylvania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elizabeth L.","family":"McMichael","sequence":"additional","affiliation":[{"name":"Department of Immunology University of Pittsburgh  Pittsburgh Pennsylvania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Uma","family":"Chandran","sequence":"additional","affiliation":[{"name":"Department of Biomedical Informatics University of Pittsburgh  Pittsburgh Pennsylvania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6605-2071","authenticated-orcid":false,"given":"Robert L.","family":"Ferris","sequence":"additional","affiliation":[{"name":"Department of Immunology University of Pittsburgh  Pittsburgh Pennsylvania"},{"name":"University of Pittsburgh Cancer Institute  Pittsburgh Pennsylvania"},{"name":"Department of Otolaryngology\u2010Head and Neck Surgery University of Pittsburgh Medical Center  Pittsburgh 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