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Analyses of dermatological irAEs have identified an association with improved overall survival (OS) following anti\u2013PD-(L)1 therapy, but the factors that contribute to this relationship are poorly understood. We collected germline whole-genome sequencing data from IMvigor211, a recent phase 3 randomized controlled trial comparing atezolizumab (anti\u2013PD-L1) monotherapy to chemotherapy in bladder cancer. We found that high vitiligo, high psoriasis, and low atopic dermatitis polygenic risk scores (PRSs) were associated with longer OS under anti\u2013PD-L1 monotherapy as compared to chemotherapy, reflecting the Th17 polarization of these diseases. PRSs were not correlated with tumor mutation burden, PD-L1 immunohistochemistry, nor T-effector gene signatures. Shared genetic factors impact risk for dermatological autoimmunity and anti\u2013PD-L1 monotherapy in bladder cancer.<\/jats:p>","DOI":"10.1073\/pnas.1922867117","type":"journal-article","created":{"date-parts":[[2020,5,19]],"date-time":"2020-05-19T17:16:15Z","timestamp":1589908575000},"page":"12288-12294","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":94,"title":["Polygenic risk for skin autoimmunity impacts immune checkpoint blockade in bladder cancer"],"prefix":"10.1073","volume":"117","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7859-3489","authenticated-orcid":false,"given":"Zia","family":"Khan","sequence":"first","affiliation":[{"name":"Genentech, South San Francisco, CA 94080;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Flavia","family":"Di Nucci","sequence":"additional","affiliation":[{"name":"Genentech, South San Francisco, CA 94080;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonia","family":"Kwan","sequence":"additional","affiliation":[{"name":"Genentech, South San Francisco, CA 94080;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Hammer","sequence":"additional","affiliation":[{"name":"Genentech, South San Francisco, CA 94080;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanjeev","family":"Mariathasan","sequence":"additional","affiliation":[{"name":"Genentech, South San Francisco, CA 94080;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincent","family":"Rouilly","sequence":"additional","affiliation":[{"name":"Genentech, South San Francisco, CA 94080;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1404-5264","authenticated-orcid":false,"given":"Jonathan","family":"Carroll","sequence":"additional","affiliation":[{"name":"Genentech, South San Francisco, CA 94080;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magnus","family":"Fontes","sequence":"additional","affiliation":[{"name":"Genentech, South San Francisco, CA 94080;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergio","family":"Ley Acosta","sequence":"additional","affiliation":[{"name":"Genentech, South San Francisco, CA 94080;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3617-5788","authenticated-orcid":false,"given":"Ellie","family":"Guardino","sequence":"additional","affiliation":[{"name":"Genentech, South San Francisco, CA 94080;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haiyin","family":"Chen-Harris","sequence":"additional","affiliation":[{"name":"Genentech, South San Francisco, CA 94080;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tushar","family":"Bhangale","sequence":"additional","affiliation":[{"name":"Genentech, South San Francisco, CA 94080;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6132-7299","authenticated-orcid":false,"given":"Ira","family":"Mellman","sequence":"additional","affiliation":[{"name":"Genentech, South San Francisco, CA 94080;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan","family":"Rosenberg","sequence":"additional","affiliation":[{"name":"Genitourinary Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Powles","sequence":"additional","affiliation":[{"name":"Barts Experimental Cancer Medicine Centre, Barts Cancer Institute, Queen Mary University of London, EC1M 6BQ London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie","family":"Hunkapiller","sequence":"additional","affiliation":[{"name":"Genentech, South San Francisco, CA 94080;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G. 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