{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T00:40:21Z","timestamp":1792456821908,"version":"4.5.0"},"reference-count":63,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T00:00:00Z","timestamp":1792368000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T00:00:00Z","timestamp":1792368000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82260593"],"award-info":[{"award-number":["82260593"]}],"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":["82460494"],"award-info":[{"award-number":["82460494"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Immunology"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Natural killer (NK) cells are innate lymphocytes, which are critical for the antitumor immunity response against tumour cells. However, the function of NK cells is frequently compromised in hepatocellular carcinoma (HCC). In this study, we found that CCAT1 expression level was reduced in peripheral blood (PB)\u2010NK cells derived from HCC patients, compared to PB\u2010NK cells derived from healthy controls. Reduced CCAT1 expression in NK cells was associated with poor disease\u2010free survival and overall survival of HCC patients. Gain\u2010 and loss\u2010of\u2010function assays revealed that CCAT1 restored NK cell cytotoxicity in\u00a0vitro and also restored NK cell antitumor activity in\u00a0vivo. Mechanistic investigations found that CCAT1 upregulated c\u2010Myc in NK cells. c\u2010Myc directly bound\n                    <jats:italic>TBX21<\/jats:italic>\n                    promoter and activated\n                    <jats:italic>TBX21<\/jats:italic>\n                    transcription, leading to the increase of T\u2010bet which is encoded by\n                    <jats:italic>TBX21<\/jats:italic>\n                    . Through upregulating c\u2010Myc, CCAT1 increased T\u2010bet expression. Functional rescue assays showed that the function of CCAT1 in NK cells was dependent on c\u2010Myc and T\u2010bet. The expression of\n                    <jats:italic>CCAT1<\/jats:italic>\n                    ,\n                    <jats:italic>MYC<\/jats:italic>\n                    and\n                    <jats:italic>TBX21<\/jats:italic>\n                    was positively correlated with each other in NK cells derived from HCC patients. Collectively, this study provided mechanistic insight into NK cell dysfunctionality in HCC and suggested that restoring CCAT1 in NK cells represented a potential NK\u2010cell\u2010targeting immunotherapeutic strategy for HCC.\n                  <\/jats:p>","DOI":"10.1111\/imm.70209","type":"journal-article","created":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T00:10:34Z","timestamp":1792455034000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["<scp>CCAT1<\/scp>\n                    Enhances\n                    <scp>NK<\/scp>\n                    Cells\u2010Mediated Antitumor Immunity in Hepatocellular Carcinoma"],"prefix":"10.1111","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-3024-1632","authenticated-orcid":false,"given":"Changke","family":"Pu","sequence":"first","affiliation":[{"name":"Department of Clinical Laboratory Affiliated Hospital of Youjiang Medical University for Nationalities  Baise China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gaoxiong","family":"Tan","sequence":"additional","affiliation":[{"name":"Graduate College of Youjiang Medical University for Nationalities  Baise China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deren","family":"Yang","sequence":"additional","affiliation":[{"name":"Graduate College of Youjiang Medical University for Nationalities  Baise China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chuan","family":"Tan","sequence":"additional","affiliation":[{"name":"The First Clinical Medical College of Jinan University  Guangzhou China"},{"name":"Department of Hepatobiliary Surgery Affiliated Hospital of Youjiang Medical University for Nationalities  Baise China"},{"name":"Guangxi Clinical Medical Research Center of Hepatobiliary Disease  Baise China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenyong","family":"Feng","sequence":"additional","affiliation":[{"name":"Graduate College of Youjiang Medical University for Nationalities  Baise China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhaolin","family":"Pan","sequence":"additional","affiliation":[{"name":"Department of Hepatobiliary Surgery Affiliated Hospital of Youjiang Medical University for Nationalities  Baise China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anmin","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Hepatobiliary Surgery Affiliated Hospital of Youjiang Medical University for Nationalities  Baise China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiajie","family":"Lin","sequence":"additional","affiliation":[{"name":"The First Clinical Medical College of Jinan University  Guangzhou China"},{"name":"Guangxi Clinical Medical Research Center of Hepatobiliary Disease  Baise China"},{"name":"Department of Orthopedics Affiliated Hospital of Youjiang Medical University for Nationalities  Baise China"},{"name":"Guangxi Zhuang Autonomous Region Engineering Research Center for Biomaterials in Bone and Joint Degenerative Diseases  Baise China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-5537-2010","authenticated-orcid":false,"given":"Chen","family":"Deng","sequence":"additional","affiliation":[{"name":"Norman Bethune International Institute of Canada for Healthcare Innovation  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4271-0847","authenticated-orcid":false,"given":"Huamei","family":"Wei","sequence":"additional","affiliation":[{"name":"Guangxi Clinical Medical Research Center of Hepatobiliary Disease  Baise China"},{"name":"Department of Pathology Affiliated Hospital of Youjiang Medical University for Nationalities  Baise China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5071-4595","authenticated-orcid":false,"given":"Jian","family":"Pu","sequence":"additional","affiliation":[{"name":"Department of Hepatobiliary Surgery Affiliated Hospital of Youjiang Medical University for Nationalities  Baise China"},{"name":"Guangxi Clinical Medical Research Center of Hepatobiliary Disease  Baise China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,19]]},"reference":[{"key":"e_1_2_10_2_1","first-page":"229","article-title":"Global Cancer Statistics 2022: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries","volume":"74","author":"Bray F.","year":"2024","journal-title":"CA: A Cancer Journal for Clinicians"},{"key":"e_1_2_10_3_1","doi-asserted-by":"crossref","first-page":"1450","DOI":"10.1056\/NEJMra1713263","article-title":"Hepatocellular 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