{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T04:46:06Z","timestamp":1790397966185,"version":"4.1.0"},"reference-count":18,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2019,4,16]],"date-time":"2019-04-16T00:00:00Z","timestamp":1555372800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100009783","name":"S:t Eriks \u00d6gonforskningsstiftelse","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100009783","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P30EY06360"],"award-info":[{"award-number":["P30EY06360"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01CA176001"],"award-info":[{"award-number":["R01CA176001"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004047","name":"Karolinska Institutet","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004047","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Medicine"],"published-print":{"date-parts":[[2019,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Survival in metastasized cutaneous melanoma (CM) has been improved with the advent of inhibitors of immune checkpoints CTLA4 and PD\u20101. In contrast, the response rate for inhibition of these checkpoints in uveal melanoma (UM) is very low. Other checkpoints including IDO and TIGIT may be targetable.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Sections from 6 patients with UM, who had undergone primary enucleation 1978\u20141995 and 6 paired liver metastases were stained immunohistochemically (SOX10, Melan\u2010A, IDO, TIGIT, and CD8). Four tumors from patients who did not develop metastasis during a mean follow\u2010up of 19\u00a0years, and 5 samples each of normal choroidal and liver tissue were included for comparison. The number of cells\/mm\n                      <jats:sup>2<\/jats:sup>\n                      expressing IDO, TIGIT and CD8 was counted with manual and digital image analysis methods. Retrospective data on patient and tumor characteristics was reviewed.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The number of TIGIT positive cells was significantly higher in primary tumors from patients who\u00a0eventually developed metastases (mean 4695\u00a0cells\/mm\n                      <jats:sup>2<\/jats:sup>\n                      ) than from patients who didn't (mean 1342\u00a0cells\/mm\n                      <jats:sup>2<\/jats:sup>\n                      ,\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0&lt;\u00a00.01) and paired metastases (463\u00a0cells\/mm\n                      <jats:sup>2<\/jats:sup>\n                      ,\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0&lt;\u00a00.01). The number of IDO positive cells was not significantly higher in metastatic tumors (\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a00.079), but the number of IDO and TIGIT positive cells\/mm\n                      <jats:sup>2<\/jats:sup>\n                      correlated in both hot spots (\n                      <jats:italic>R<\/jats:italic>\n                      <jats:sup>2<\/jats:sup>\n                      \u00a0=\u00a00.24,\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0&lt;\u00a00.01) and full tumor sections (\n                      <jats:italic>R<\/jats:italic>\n                      <jats:sup>2<\/jats:sup>\n                      \u00a0=\u00a00.35,\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0&lt;\u00a00.01).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The expression of immune checkpoint receptor TIGIT is increased in primary uveal melanomas that seed metastases, and correlates with the expression of checkpoint receptor IDO. Both may be future targets for therapy.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cam4.2167","type":"journal-article","created":{"date-parts":[[2019,4,16]],"date-time":"2019-04-16T22:19:56Z","timestamp":1555453196000},"page":"2784-2792","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":54,"title":["Expression of immune checkpoint receptors Indoleamine 2,3\u2010dioxygenase and T cell Ig and ITIM domain in metastatic versus nonmetastatic choroidal melanoma"],"prefix":"10.1002","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9401-8911","authenticated-orcid":false,"given":"Gustav","family":"St\u00e5lhammar","sequence":"first","affiliation":[{"name":"St. Erik Eye Hospital Stockholm Sweden"},{"name":"Department of Clinical Neuroscience Karolinska Institutet Stockholm Sweden"},{"name":"Departments of Ophthalmology and Pathology Emory University School of Medicine Atlanta Georgia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Seregard","sequence":"additional","affiliation":[{"name":"St. Erik Eye Hospital Stockholm Sweden"},{"name":"Department of Clinical Neuroscience Karolinska Institutet Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans E.","family":"Grossniklaus","sequence":"additional","affiliation":[{"name":"Departments of Ophthalmology and Pathology Emory University School of Medicine Atlanta Georgia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,4,16]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-642-54255-8_6"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2015.09.013"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1504030"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ctrv.2017.08.009"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.2217\/fon-2018-0116"},{"key":"e_1_2_10_7_1","first-page":"5712","article-title":"Lack of BRAF mutations in uveal melanoma","volume":"63","author":"Rimoldi D","year":"2003","journal-title":"Can Res"},{"issue":"204","key":"e_1_2_10_8_1","first-page":"e215","article-title":"Integrative analysis identifies four molecular and clinical subsets in uveal melanoma","volume":"32","author":"Robertson AG","year":"2017","journal-title":"Cancer Cell"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.2217\/imt-2017-0066"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1080\/2162402X.2017.1321187"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2012.10.001"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1097\/PPO.0b013e3181eb3343"},{"key":"e_1_2_10_13_1","first-page":"48","article-title":"The surface protein TIGIT suppresses T cell activation by promoting the generation of mature immunoregulatory dendritic cells","volume":"10","author":"Xin Y","year":"2008","journal-title":"Nat Immunol"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI80445"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/imr.12518"},{"key":"e_1_2_10_16_1","unstructured":"Kivel\u00e4T SimpsonER GrossniklausHEet al.Uveal Melanoma. 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