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This combined strategy boosted NK cell effector function through enhancing the Akt\/mTORC1 axis and c-MYC signaling, resulting in increased aerobic glycolysis. When tested in a lymphoma mouse model, this combined approach improved NK cell antitumor activity more than either alteration alone, eradicating lymphoma xenografts without signs of any measurable toxicity. We conclude that targeting a cytokine checkpoint further enhances the antitumor activity of IL-15\u2013secreting armored CAR-NK cells by promoting their metabolic fitness and antitumor activity. This combined approach represents a promising milestone in the development of the next generation of NK cells for cancer immunotherapy.<\/jats:p>","DOI":"10.1182\/blood.2020007748","type":"journal-article","created":{"date-parts":[[2020,9,9]],"date-time":"2020-09-09T14:08:16Z","timestamp":1599660496000},"page":"624-636","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":269,"title":["Targeting a cytokine checkpoint enhances the fitness of armored cord blood CAR-NK cells"],"prefix":"10.1182","volume":"137","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6026-8397","authenticated-orcid":false,"given":"May","family":"Daher","sequence":"first","affiliation":[{"name":"Department of Stem Cell Transplantation and Cellular Therapy and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rafet","family":"Basar","sequence":"additional","affiliation":[{"name":"Department of Stem Cell Transplantation and Cellular Therapy 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