{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T17:29:48Z","timestamp":1783531788524,"version":"3.55.0"},"reference-count":32,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2020,10,30]],"date-time":"2020-10-30T00:00:00Z","timestamp":1604016000000},"content-version":"vor","delay-in-days":303,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100010590","name":"Tianjin Municipal Bureau of Public Health","doi-asserted-by":"publisher","award":["15KG145"],"award-info":[{"award-number":["15KG145"]}],"id":[{"id":"10.13039\/501100010590","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81670184"],"award-info":[{"award-number":["81670184"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81770213"],"award-info":[{"award-number":["81770213"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006606","name":"Natural Science Foundation of Tianjin Municipality","doi-asserted-by":"publisher","award":["18JCZDJC45100"],"award-info":[{"award-number":["18JCZDJC45100"]}],"id":[{"id":"10.13039\/501100006606","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006606","name":"Natural Science Foundation of Tianjin Municipality","doi-asserted-by":"publisher","award":["19JCYBJC26500"],"award-info":[{"award-number":["19JCYBJC26500"]}],"id":[{"id":"10.13039\/501100006606","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Immunology Research"],"published-print":{"date-parts":[[2020,1]]},"abstract":"<jats:p>\n                    Tim\u20103 is a promising target for antitumor immunotherapy. A number of clinical trials are evaluating the efficacy of anti\u2010Tim\u20103 therapies as a single agent or combinations in solid tumors and haematologic malignancies. However, there remains a considerable lack of data on Tim\u20103 signalling, especially the genetic characteristics and immune microenvironment, in diffuse large B cell lymphoma (DLBCL). Herein, we identified three genetic mutations in galectin\u20109, a major ligand of Tim\u20103, in six patients with DLBCL (6\/188, 3.2%) that were not detected in the COSMIC database. The Oncomine database showed that the mRNA levels of Tim\u20103 were higher in DLBCL cells than those in normal B cells. Multiplexed immunofluorescence revealed that patients with Tim\u20103\u2010expressing tumor\u2010infiltrating lymphocytes (Tim\u20103\n                    <jats:sup>+<\/jats:sup>\n                    TILs) exhibited poor outcomes than those with Tim\u20103\n                    <jats:sup>-<\/jats:sup>\n                    TILs (\n                    <jats:italic>p<\/jats:italic>\n                    = 0.041). The median survival times of these patients were 65.0 (95% confidence interval (CI): 71.2\u201388.6) and 79.9 months (95% CI: 54.4\u201375.6), respectively. Furthermore, we defined a novel subtype of exhausted T cells, named as exhausted Tim\u20103\n                    <jats:sup>+<\/jats:sup>\n                    CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells, and found that patients with exhausted Tim\u20103\n                    <jats:sup>+<\/jats:sup>\n                    CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells (median survival, 62.8 months, 95% CI: 50.0\u201375.6) exhibited shorter survival than those with nonexhausted Tim\u20103\n                    <jats:sup>-<\/jats:sup>\n                    CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells (median survival, 82.5 months, 95% CI: 72.0\u201392.9;\n                    <jats:italic>p<\/jats:italic>\n                    = 0.034). Overall, these findings provide the genetic status of the Tim\u20103 ligand in DLBCL. Patients with Tim\u20103\n                    <jats:sup>+<\/jats:sup>\n                    TILs and exhausted Tim\u20103\n                    <jats:sup>+<\/jats:sup>\n                    CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells exhibited inferior survival, thus highlighting the possibility of potential therapeutic applications of the inhibition of Tim\u20103 alone or in combination with other immune checkpoints for treatment of patients with DLBCL.\n                  <\/jats:p>","DOI":"10.1155\/2020\/6968595","type":"journal-article","created":{"date-parts":[[2020,10,30]],"date-time":"2020-10-30T14:35:13Z","timestamp":1604068513000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Genetic Mutations of Tim\u20103 Ligand and Exhausted Tim\u20103\n                    <sup>+<\/sup>\n                    CD8\n                    <sup>+<\/sup>\n                    T Cells and Survival in Diffuse Large B Cell Lymphoma"],"prefix":"10.1155","volume":"2020","author":[{"given":"Tingting","family":"Zhang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianyuan","family":"Ren","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zheng","family":"Song","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Jiao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenzhen","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xianming","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lihua","family":"Qiu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3030-1739","authenticated-orcid":false,"given":"Lanfang","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiyong","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Meng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiongli","family":"Zhai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiubao","family":"Ren","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4684-6250","authenticated-orcid":false,"given":"Zhengzi","family":"Qian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7663-2923","authenticated-orcid":false,"given":"Xianhuo","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8558-3131","authenticated-orcid":false,"given":"Huilai","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,10,30]]},"reference":[{"key":"e_1_2_9_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.pathol.2017.09.006"},{"key":"e_1_2_9_2_2","doi-asserted-by":"publisher","DOI":"10.2147\/OTT.S53164"},{"key":"e_1_2_9_3_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.18.00766"},{"key":"e_1_2_9_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.semcancer.2017.10.001"},{"key":"e_1_2_9_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni987"},{"key":"e_1_2_9_6_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20100637"},{"key":"e_1_2_9_7_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI46102"},{"key":"e_1_2_9_8_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20100643"},{"key":"e_1_2_9_9_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2010-10-310425"},{"key":"e_1_2_9_10_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms18030645"},{"key":"e_1_2_9_11_2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-11-0096"},{"key":"e_1_2_9_12_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2008-12-195792"},{"key":"e_1_2_9_13_2","doi-asserted-by":"publisher","DOI":"10.1093\/intimm\/dxm044"},{"key":"e_1_2_9_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.2514"},{"key":"e_1_2_9_15_2","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.32144"},{"key":"e_1_2_9_16_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature21349"},{"key":"e_1_2_9_17_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12185-018-2466-7"},{"key":"e_1_2_9_18_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00428-013-1519-9"},{"key":"e_1_2_9_19_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1305133"},{"key":"e_1_2_9_20_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0030676"},{"key":"e_1_2_9_21_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI59806"},{"key":"e_1_2_9_22_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm.2871"},{"key":"e_1_2_9_23_2","doi-asserted-by":"publisher","DOI":"10.2217\/imt-2017-0024"},{"key":"e_1_2_9_24_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-53216-z"},{"key":"e_1_2_9_25_2","doi-asserted-by":"publisher","DOI":"10.1007\/s13277-014-2080-0"},{"key":"e_1_2_9_26_2","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.26771"},{"key":"e_1_2_9_27_2","doi-asserted-by":"publisher","DOI":"10.1158\/2326-6066.CIR-15-0210"},{"key":"e_1_2_9_28_2","doi-asserted-by":"publisher","DOI":"10.1309\/AJCP9Q6OVLVSHTMY"},{"key":"e_1_2_9_29_2"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