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We developed a series of mouse models that carry genotypes of human HGSCs and grow in syngeneic immunocompetent hosts to address this gap. We transformed murine-fallopian tube epithelial cells to phenocopy homologous recombination\u2013deficient tumors through a combined loss of Trp53, Brca1, Pten, and Nf1 and overexpression of Myc and Trp53R172H, which was contrasted with an identical model carrying wild-type Brca1. For homologous recombination\u2013proficient tumors, we constructed genotypes combining loss of Trp53 and overexpression of Ccne1, Akt2, and Trp53R172H, and driven by KRASG12V or Brd4 or Smarca4 overexpression. These lines form tumors recapitulating human disease, including genotype-driven responses to treatment, and enabled us to identify follistatin as a driver of resistance to checkpoint inhibitors. These data provide proof of concept that our models can identify new immunotherapy targets in HGSC.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Significance:<\/jats:title>\n                    <jats:p>We engineered a panel of murine fallopian tube epithelial cells bearing mutations typical of HGSC and capable of forming tumors in syngeneic immunocompetent hosts. These models recapitulate tumor microenvironments and drug responses characteristic of human disease. In a Ccne1-overexpressing model, immune-checkpoint resistance was driven by follistatin.<\/jats:p>\n                    <jats:p>This article is highlighted in the In This Issue feature, p. 211<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1158\/2159-8290.cd-20-0818","type":"journal-article","created":{"date-parts":[[2020,11,6]],"date-time":"2020-11-06T14:40:15Z","timestamp":1604673615000},"page":"384-407","update-policy":"https:\/\/doi.org\/10.1158\/crossmark_policy","source":"Crossref","is-referenced-by-count":143,"title":["Genetically Defined Syngeneic Mouse Models of Ovarian Cancer as Tools for the Discovery of Combination Immunotherapy"],"prefix":"10.1158","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3840-5583","authenticated-orcid":false,"given":"Sonia","family":"Iyer","sequence":"first","affiliation":[{"name":"1Whitehead Institute for Biomedical Research, Cambridge, Massachusetts."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuang","family":"Zhang","sequence":"additional","affiliation":[{"name":"2Laura and Isaac Perlmutter Cancer Center, NYU-Langone Medical Center, New York, New York."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simge","family":"Yucel","sequence":"additional","affiliation":[{"name":"1Whitehead Institute for Biomedical Research, Cambridge, Massachusetts."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4898-0557","authenticated-orcid":false,"given":"Heiko","family":"Horn","sequence":"additional","affiliation":[{"name":"3Stanley Center, Broad Institute of MIT and Harvard, Cambridge, Massachusetts."},{"name":"4Pediatric Surgical Research Laboratories, Massachusetts General Hospital; Department of Surgery, Harvard Medical School, Boston, Massachusetts."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sean G.","family":"Smith","sequence":"additional","affiliation":[{"name":"5Marble Center for Cancer Nanomedicine, Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ferenc","family":"Reinhardt","sequence":"additional","affiliation":[{"name":"1Whitehead Institute for Biomedical Research, Cambridge, Massachusetts."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esmee","family":"Hoefsmit","sequence":"additional","affiliation":[{"name":"1Whitehead Institute for Biomedical Research, Cambridge, Massachusetts."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6813-5169","authenticated-orcid":false,"given":"Bimarzhan","family":"Assatova","sequence":"additional","affiliation":[{"name":"1Whitehead Institute for Biomedical Research, Cambridge, Massachusetts."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3662-8794","authenticated-orcid":false,"given":"Julia","family":"Casado","sequence":"additional","affiliation":[{"name":"6Research Program in Systems Oncology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie-Charlotte","family":"Meinsohn","sequence":"additional","affiliation":[{"name":"4Pediatric Surgical Research Laboratories, Massachusetts General Hospital; Department of Surgery, Harvard Medical School, Boston, Massachusetts."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. 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