{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T18:34:07Z","timestamp":1793471647488,"version":"4.5.0"},"reference-count":30,"publisher":"American Society for Clinical Investigation","issue":"16","funder":[{"name":"NIH","award":["NIH: R01-CA198482 (WKR),K24-CA172355 (WKR),T32-CA009582-28 (AAD),P30-CA072720 (AP"],"award-info":[{"award-number":["NIH: R01-CA198482 (WKR),K24-CA172355 (WKR),T32-CA009582-28 (AAD),P30-CA072720 (AP"]}]},{"name":"U.S. Department of Defense","award":["DOD-CA160728P1"],"award-info":[{"award-number":["DOD-CA160728P1"]}]},{"name":"Cancer Research Institute","award":["Irvington Fellowship"],"award-info":[{"award-number":["Irvington Fellowship"]}]},{"name":"National Science Foundation","award":["PHY-1607611"],"award-info":[{"award-number":["PHY-1607611"]}]},{"DOI":"10.13039\/100002338","name":"Val Skinner Foundation","doi-asserted-by":"crossref","award":["NA"],"award-info":[{"award-number":["NA"]}],"id":[{"id":"10.13039\/100002338","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2018,8,23]]},"abstract":"<jats:p>\n                    Although a subset of clear cell renal cell carcinoma (ccRCC) patients respond to immune checkpoint blockade (ICB), predictors of response remain uncertain. We investigated whether abnormal expression of endogenous retroviruses (ERVs) in tumors is associated with local immune checkpoint activation (ICA) and response to ICB. Twenty potentially immunogenic ERVs (\u03c0ERVs) were identified in ccRCC in The Cancer Genome Atlas data set, and tumors were stratified into 3 groups based on their expression levels. \u03c0ERV-high ccRCC tumors showed increased immune infiltration, checkpoint pathway upregulation, and higher CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cell fraction in infiltrating leukocytes compared with \u03c0ERV-low ccRCC tumors. Similar results were observed in ER\n                    <jats:sup>+<\/jats:sup>\n                    \/HER2\n                    <jats:sup>\u2212<\/jats:sup>\n                    breast, colon, and head and neck squamous cell cancers. ERV expression correlated with expression of genes associated with histone methylation and chromatin regulation, and \u03c0ERV-high ccRCC was enriched in\n                    <jats:italic>BAP1<\/jats:italic>\n                    mutant tumors.\n                    <jats:italic>ERV3-2<\/jats:italic>\n                    expression correlated with ICA in 11 solid cancers, including the 4 named above. In a small retrospective cohort of 24 metastatic ccRCC patients treated with single-agent PD-1\/PD-L1 blockade,\n                    <jats:italic>ERV3-2<\/jats:italic>\n                    expression in tumors was significantly higher in responders compared with nonresponders. Thus, abnormal expression of \u03c0ERVs is associated with ICA in several solid cancers, including ccRCC, and\n                    <jats:italic>ERV3-2<\/jats:italic>\n                    expression is associated with response to ICB in ccRCC.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.121522","type":"journal-article","created":{"date-parts":[[2018,8,22]],"date-time":"2018-08-22T11:01:09Z","timestamp":1534935669000},"source":"Crossref","is-referenced-by-count":182,"title":["Endogenous retrovirus expression is associated with response to immune checkpoint blockade in clear cell renal cell carcinoma"],"prefix":"10.1172","volume":"3","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7917-0317","authenticated-orcid":true,"given":"Anshuman","family":"Panda","sequence":"first","affiliation":[{"name":"Rutgers Cancer Institute of New Jersey, New Brunswick, New Jersey, USA."},{"name":"Department of Physics and Astronomy, Rutgers University, Piscataway, New Jersey, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aguirre A.","family":"de Cubas","sequence":"additional","affiliation":[{"name":"Vanderbilt-Ingram Cancer Center, Nashville, Tennessee, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Stein","sequence":"additional","affiliation":[{"name":"Rutgers Cancer Institute of New Jersey, New Brunswick, New Jersey, USA."},{"name":"Rutgers Robert Wood Johnson Medical School, New Brunswick, New Jersey, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregory","family":"Riedlinger","sequence":"additional","affiliation":[{"name":"Rutgers Cancer Institute of New Jersey, New Brunswick, New Jersey, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshua","family":"Kra","sequence":"additional","affiliation":[{"name":"Rutgers Cancer Institute of New Jersey, New Brunswick, New Jersey, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tina","family":"Mayer","sequence":"additional","affiliation":[{"name":"Rutgers Cancer Institute of New Jersey, New Brunswick, New Jersey, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christof C.","family":"Smith","sequence":"additional","affiliation":[{"name":"Department of Medicine, Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin G.","family":"Vincent","sequence":"additional","affiliation":[{"name":"Department of Medicine, Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4568-1092","authenticated-orcid":true,"given":"Jonathan S.","family":"Serody","sequence":"additional","affiliation":[{"name":"Department of Medicine, Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathryn E.","family":"Beckermann","sequence":"additional","affiliation":[{"name":"Vanderbilt-Ingram Cancer Center, Nashville, Tennessee, USA."},{"name":"Department of Medicine, Division of Hematology and Oncology, Vanderbilt University Medical Center, Nashville, Tennessee, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shridar","family":"Ganesan","sequence":"additional","affiliation":[{"name":"Rutgers Cancer Institute of New Jersey, New Brunswick, New Jersey, USA."},{"name":"Rutgers Robert Wood Johnson Medical School, New Brunswick, New Jersey, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7822-5259","authenticated-orcid":true,"given":"Gyan","family":"Bhanot","sequence":"additional","affiliation":[{"name":"Rutgers Cancer Institute of New Jersey, New Brunswick, New Jersey, USA."},{"name":"Department of Physics and Astronomy, Rutgers University, Piscataway, New Jersey, USA."},{"name":"Department of Molecular Biology and Biochemistry, Rutgers University, Piscataway, New Jersey, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"W. Kimryn","family":"Rathmell","sequence":"additional","affiliation":[{"name":"Vanderbilt-Ingram Cancer Center, Nashville, Tennessee, USA."},{"name":"Department of Medicine, Division of Hematology and Oncology, Vanderbilt University Medical Center, Nashville, Tennessee, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"232","published-online":{"date-parts":[[2018,8,23]]},"reference":[{"key":"B1","first-page":"15","article-title":"Prospects for targeting PD-1 and PD-L1 in various tumor types","volume":"28 Suppl 3","author":"Kim","year":"2014","journal-title":"Oncology (Williston Park, 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