{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T06:29:55Z","timestamp":1787725795056,"version":"build-2784847793"},"reference-count":51,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2024,3,2]],"date-time":"2024-03-02T00:00:00Z","timestamp":1709337600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31800737"],"award-info":[{"award-number":["31800737"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2024,3,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    CD3\n                    <jats:sup>+<\/jats:sup>\n                    CD56\n                    <jats:sup>+<\/jats:sup>\n                    NKT\u2010like cells are crucial to antitumor immune surveillance and defense. However, research on circulating NKT\u2010like cells in colorectal cancer (CRC) patients is limited. This investigation selected 113 patients diagnosed with primary CRC for preoperative peripheral blood collection. The blood from 106 healthy donors at the physical examination center was acquired as a healthy control (HC). The distribution of lymphocyte subsets, immunophenotype, and functional characteristics of NKT\u2010like cells was comprehensively evaluated. Compared to HC, primary CRC patients had considerably fewer peripheral NKT\u2010like cells in frequency and absolute quantity, and the fraction of NKT\u2010like cells was further reduced in patients with vascular invasion compared to those without. The NKT\u2010like cells in CRC patients had a reduced fraction of the activating receptor CD16, up\u2010regulated expression of inhibitory receptors LAG\u20103 and NKG2A, impaired production of TNF\u2010\u03b1 and IFN\u2010\u03b3, as well as degranulation capacity. Moreover, the increased frequency of NKG2A\n                    <jats:sup>+<\/jats:sup>\n                    NKT\u2010like cells and the decreased expression of activation\u2010related molecules were significantly correlated with tumor progression. In detail, NKG2A\n                    <jats:sup>+<\/jats:sup>\n                    NKT\u2010like cells indicated increased PD\u20101 and Tim\u20103 and reduced TNF\u2010\u03b1 than NKG2A\n                    <jats:sup>\u2212<\/jats:sup>\n                    subgroup. Blocking NKG2A in\u00a0vitro restored cytokine secretion capacity in NKT\u2010like cells from CRC patients. Altogether, this research revealed that circulating NKT\u2010like cells in CRC patients exhibited suppressive phenotype and functional impairment, which was more pronounced in NKG2A\n                    <jats:sup>+<\/jats:sup>\n                    NKT\u2010like cells. These findings suggest that NKG2A blockade may restore anti\u2010tumor effector function in NKT\u2010like cells, which provides a potential target for immunotherapy in CRC patients.\n                  <\/jats:p>","DOI":"10.1096\/fj.202301743r","type":"journal-article","created":{"date-parts":[[2024,3,2]],"date-time":"2024-03-02T10:54:26Z","timestamp":1709376866000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Phenotypic and functional exhaustion of circulating\n                    <scp>CD3<\/scp>\n                    <sup>+<\/sup>\n                    <scp>CD56<\/scp>\n                    <sup>+<\/sup>\n                    <scp>NKT<\/scp>\n                    \u2010like cells in colorectal cancer patients"],"prefix":"10.1096","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-3486-9837","authenticated-orcid":false,"given":"Kangli","family":"Cao","sequence":"first","affiliation":[{"name":"Department 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