{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T18:12:01Z","timestamp":1779214321538,"version":"3.51.4"},"reference-count":51,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2019,5,1]],"date-time":"2019-05-01T00:00:00Z","timestamp":1556668800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,5,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>The clinical benefit of CTLA-4 blockade on T cells is known, yet the impact of its expression on cancer cells remains unaddressed. We define an immunosuppressive role for tumor-expressed CTLA-4 using chronic lymphocytic leukemia (CLL) as a disease model. CLL cells, among other cancer cells, are CTLA-4+. Coculture with activated human T cells induced surface CTLA-4 on primary human CLL B cells. CTLA-4 on CLL-derived human cell lines decreased CD80 expression on cocultured CD80+ cells, with restoration upon CTLA-4 blockade. Coculture of CTLA-4+ CLL cells with CD80-GFP+ cell lines revealed transfer of CD80-GFP into CLL tumor cells, similar to CTLA-4+ T cells able to trans-endocytose CD80. Coculture of T cells with CTLA-4+ CLL cells decreased IL-2 production. Using a human CTLA-4 knock-in mouse lacking Fc\u03b3R function, antitumor efficacy was observed by blocking murine CTLA-4 on tumor cells in isolation of the T cell effect and Fc-mediated depletion. These data implicate tumor CTLA-4 in cancer cell\u2013mediated immunosuppression in vitro and as having a functional role in tumor cells in vivo.<\/jats:p>","DOI":"10.4049\/jimmunol.1801359","type":"journal-article","created":{"date-parts":[[2019,3,25]],"date-time":"2019-03-25T18:35:30Z","timestamp":1553538930000},"page":"2806-2816","source":"Crossref","is-referenced-by-count":32,"title":["Leukemic B Cell CTLA-4 Suppresses Costimulation of T Cells"],"prefix":"10.1093","volume":"202","author":[{"given":"Priscilla","family":"Do","sequence":"first","affiliation":[{"name":"Biomedical Sciences Graduate Program, The Ohio State University , Columbus, OH 43210"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8025-2512","authenticated-orcid":false,"given":"Kyle A","family":"Beckwith","sequence":"additional","affiliation":[{"name":"Biomedical Sciences Graduate Program, The Ohio State University , Columbus, OH 43210"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9697-7585","authenticated-orcid":false,"given":"Carolyn","family":"Cheney","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Comprehensive Cancer Center, The Ohio State University , Columbus, OH 43210"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Minh","family":"Tran","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Comprehensive Cancer Center, The Ohio State University , Columbus, OH 43210"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Larry","family":"Beaver","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Comprehensive Cancer Center, The Ohio State University , Columbus, OH 43210"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brittany G","family":"Griffin","sequence":"additional","affiliation":[{"name":"Hendrix College , Conway, AR 72032"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaokui","family":"Mo","sequence":"additional","affiliation":[{"name":"Center for Biostatistics, Comprehensive Cancer Center, The Ohio State University , Columbus, OH 43210"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yang","family":"Liu","sequence":"additional","affiliation":[{"name":"Children\u2019s National Health System , Washington, DC 20010"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rosa","family":"Lapalombella","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Comprehensive Cancer Center, The Ohio State University , Columbus, OH 43210"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Erin","family":"Hertlein","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Comprehensive Cancer Center, The Ohio State University , Columbus, OH 43210"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0351-4504","authenticated-orcid":false,"given":"Natarajan","family":"Muthusamy","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Comprehensive Cancer Center, The Ohio State University , Columbus, OH 43210"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John C","family":"Byrd","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Comprehensive Cancer Center, The Ohio State University , Columbus, OH 43210"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2019,5,1]]},"reference":[{"key":"2025030417561912100_r1","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1038\/328267a0","article-title":"A new member of the immunoglobulin superfamily--CTLA-4","volume":"328","author":"Brunet","year":"1987","journal-title":"Nature"},{"key":"2025030417561912100_r2","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1038\/nri727","article-title":"The B7-CD28 superfamily","volume":"2","author":"Sharpe","year":"2002","journal-title":"Nat. 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