{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T14:22:45Z","timestamp":1788531765343,"version":"build-2803163510"},"reference-count":35,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T00:00:00Z","timestamp":1787702400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"Wuhan Health Commission Research Foundation","award":["WX23A32"],"award-info":[{"award-number":["WX23A32"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,8,27]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Natural killer (NK) cells are active tumoricidal cells that inhibit esophageal cancer (EC) development, making them a prospective immunotherapeutic tool. Nonetheless, NK cells undergo both activation and exhaustion in the tumor microenvironment, but the related mechanisms have not been thoroughly understood. Using a chemical-induced EC model, we investigated the expression pattern and functional properties of zinc finger protein 600 (ZNF600) in EC-associated NK cells. For the first time, we revealed that ZNF600 expression was diminished in EC-associated NK cells, particularly those exhibiting the exhaustion phenotype. In vitro silencing of ZNF600 resulted in a remarkable downregulation of tumor necrosis factor, interferon-gamma, and cytolytic perforin and granzyme B, leading to an impairment of NK cell tumoricidal capacity. On the contrary, ZNF600 overexpression promoted NK cell tumoricidal capacity. Adoptive transfer of ZNF600-overexpressing NK cells significantly inhibited the growth of EC implants. Furthermore, EC cells significantly downregulated ZNF600 in NK cells. Interestingly, neutralizing carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) and T-cell immunoglobulin and mucin-domain containing-3 (TIM-3) partially restored ZNF600 expression after co-culture with EC cells. Conclusively, the CEACAM1-TIM-3 signaling axis might decrease ZNF600 in EC-associated NK cells and subsequently suppress NK cell-mediated killing of EC cells. This research discovers a novel mechanism by which the EC microenvironment induces NK cell dysfunction.<\/jats:p>","DOI":"10.1093\/jleuko\/qiag119","type":"journal-article","created":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T11:34:27Z","timestamp":1787657667000},"source":"Crossref","is-referenced-by-count":0,"title":["Zinc finger protein 600 is essential for the cytotoxic function of esophageal cancer-associated natural killer cells"],"prefix":"10.1093","volume":"118","author":[{"given":"Jiongming","family":"He","sequence":"first","affiliation":[{"name":"Department of Thoracic Surgery, Wuhan Third Hospital (Tongren Hospital of Wuhan University) Shouyi Campus , 241 Pengliuyang Road, Wuchang District, Wuhan, Hubei Province 430060 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shan","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery, Wuhan Third Hospital (Tongren Hospital of Wuhan University) Guanggu Campus , 216 Guanshan Street, Hongshan District, Wuhan, Hubei Province 430073 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lingying","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Thyroid and Breast Surgery, Wuhan Third Hospital (Tongren Hospital of Wuhan University) Guanggu Campus , 216 Guanshan Street, Hongshan District, Wuhan, Hubei Province 430073 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-6191-9037","authenticated-orcid":false,"given":"Fei","family":"Xiong","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery, Wuhan Third Hospital (Tongren Hospital of Wuhan University) Guanggu Campus , 216 Guanshan Street, Hongshan District, Wuhan, Hubei Province 430073 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