{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T16:11:19Z","timestamp":1790871079775,"version":"4.1.0"},"reference-count":44,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2025,1,7]],"date-time":"2025-01-07T00:00:00Z","timestamp":1736208000000},"content-version":"vor","delay-in-days":737,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,1,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>NK cells are major effector cells involved in the elimination of early tumors and prevent metastasis. They often have an impaired function in patients with cancer. Preclinical studies have demonstrated NK cell activation as the adjunctive effect of invariant NKT (iNKT) cells. Activation of iNKT cells after administration of the glycolipid ligand \u03b1-galactosylceramide, loaded with CD1d-expressing human PBMC-derived APCs (APC\/Gal), is an attractive cancer therapy to optimize the use of NK cells. However, the subsets of NK cells that are activated following iNKT cell activation as well as the period of NK cell activation remain unclear. In this study, we report that the granzyme B\u2013expressing NK cell response in postoperative lung cancer patients was enhanced 49 d after administration of APC\/Gal in a phase II study. We found maximum IFN-\u03b3 production on day 49 in 13 out of 27 APC\/Gal-treated patients. On day 49, 14 out of 27 patients (51.9%) had higher IFN-\u03b3 production by iNKT cells (&amp;gt;6-fold higher than the baseline level). This increment significantly correlated with granzyme B\u2013expressing NK cells. Although IFN-\u03b3 production was lower in patients in the nontreated group, we detected maximum IFN-\u03b3 production 12 mo after the resection of lung cancer (9 out of 29 patients [31%]). These findings suggest that elimination of cancer cells leads to increased NK cell function, which can be further enhanced by APC\/Gal therapy.<\/jats:p>","DOI":"10.4049\/immunohorizons.2200091","type":"journal-article","created":{"date-parts":[[2023,1,13]],"date-time":"2023-01-13T15:31:40Z","timestamp":1673623900000},"page":"1-16","source":"Crossref","is-referenced-by-count":6,"title":["Augmenting Granzyme B\u2013Expressing NK Cells by Invariant NKT Ligand\u2013Loaded APCs in Patients with Postoperative Early Stage Non\u2013Small Cell Lung Cancer: Results of a Randomized Phase II Study"],"prefix":"10.1093","volume":"7","author":[{"given":"Tomonori","family":"Iyoda","sequence":"first","affiliation":[{"name":"Laboratory for Immunotherapy, RIKEN Center for Integrative Medical Sciences , Yokohama ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kanako","family":"Shimizu","sequence":"additional","affiliation":[{"name":"Laboratory for Immunotherapy, RIKEN Center for Integrative Medical Sciences , Yokohama ,","place":["Japan"]},{"name":"RIKEN Drug Discovery and Medical Technology Platforms , Yokohama ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masami","family":"Kawamura","sequence":"additional","affiliation":[{"name":"Laboratory for Immunotherapy, RIKEN Center for Integrative Medical Sciences , Yokohama ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Shinga","sequence":"additional","affiliation":[{"name":"Laboratory for Immunotherapy, RIKEN Center for Integrative Medical Sciences , Yokohama ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6184-0375","authenticated-orcid":false,"given":"Takashi","family":"Watanabe","sequence":"additional","affiliation":[{"name":"Laboratory for Integrative Genomics, RIKEN Center for Integrative Medical Sciences , Yokohama ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5241-6062","authenticated-orcid":false,"given":"Koya","family":"Fukunaga","sequence":"additional","affiliation":[{"name":"Laboratory for Pharmacogenomics, RIKEN Center for Integrative Medical Sciences , Yokohama ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4139-8794","authenticated-orcid":false,"given":"Taisei","family":"Mushiroda","sequence":"additional","affiliation":[{"name":"Laboratory for Pharmacogenomics, RIKEN Center for Integrative Medical Sciences , Yokohama ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hideo","family":"Saka","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine, Nagoya Medical Center, National Hospital Organization , Nagoya ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiyoe","family":"Kitagawa","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Nagoya Medical Center, National Hospital Organization , Nagoya ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shin-ichiro","family":"Shimamatsu","sequence":"additional","affiliation":[{"name":"Department of Thoracic Oncology, Kyushu Cancer Center, National Hospital Organization , Fukuoka ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mitsuhiro","family":"Takenoyama","sequence":"additional","affiliation":[{"name":"Department of Thoracic Oncology, Kyushu Cancer Center, National Hospital Organization , Fukuoka ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Youko","family":"Suehiro","sequence":"additional","affiliation":[{"name":"Department of Hematology, Kyushu Cancer Center, National Hospital Organization , Fukuoka ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takumi","family":"Imai","sequence":"additional","affiliation":[{"name":"Department of Medical Statistics, Graduate School of Medicine, Osaka Metropolitan University , Osaka ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayumi","family":"Shintani","sequence":"additional","affiliation":[{"name":"Department of Medical Statistics, Graduate School of Medicine, Osaka Metropolitan University , Osaka ,","place":["Japan"]},{"name":"Department of Clinical Research, Clinical Research Center, National Hospital Organization , Tokyo ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suminobu","family":"Ito","sequence":"additional","affiliation":[{"name":"Department of Clinical Research, Clinical Research Center, National Hospital Organization , Tokyo ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3586-3976","authenticated-orcid":false,"given":"Shin-ichiro","family":"Fujii","sequence":"additional","affiliation":[{"name":"Laboratory for Immunotherapy, RIKEN Center for Integrative Medical Sciences , Yokohama ,","place":["Japan"]},{"name":"RIKEN Drug Discovery and Medical Technology Platforms , Yokohama ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2023,1,13]]},"reference":[{"key":"2025010703543461300_r1","doi-asserted-by":"crossref","first-page":"394","DOI":"10.3322\/caac.21492","article-title":"Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. [Published erratum appears in 2020 CA Cancer J. Clin. 70: 313.]","volume":"68","author":"Bray","year":"2018","journal-title":"CA Cancer J. Clin"},{"key":"2025010703543461300_r2","first-page":"242","article-title":"Recurrence after surgery in patients with NSCLC","volume":"3","author":"Uramoto","year":"2014","journal-title":"Transl. Lung Cancer Res"},{"key":"2025010703543461300_r3","doi-asserted-by":"crossref","first-page":"2656","DOI":"10.21037\/tlcr-20-546","article-title":"Integrating immune checkpoint inhibitors and targeted therapies in the treatment of early stage non-small cell lung cancer: a narrative review","volume":"9","author":"Ortega-Franco","year":"2020","journal-title":"Transl. Lung Cancer Res"},{"key":"2025010703543461300_r4","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1038\/s41423-020-00577-5","article-title":"The cutting-edge progress of immune-checkpoint blockade in lung cancer","volume":"18","author":"Zhou","year":"2021","journal-title":"Cell. Mol. 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