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Despite their success in hematologic malignancies, NK cell\u2010based therapies have been limited in the context of solid tumors. Tumor cells undergo various metabolic adaptations to sustain the immense energy demands that are needed to support their rapid and uncontrolled proliferation. As a result, the tumor microenvironment (TME) is depleted of nutrients needed to fuel immune cell activity and contains several immunosuppressive metabolites that hinder NK cell antitumor functions. Further, we now know that NK cell metabolic status is a main determining factor of their effector functions. Hence, the ability of NK cells to withstand and adapt to these metabolically hostile conditions is imperative for effective and sustained antitumor activity in the TME. With this in mind, we review the consequences of metabolic hostility in the TME on NK cell metabolism and function. We also discuss tumor\u2010like metabolic programs in NK cell induced by STAT3\u2010mediated expansion that adapt NK cells to thrive in the TME. Finally, we examine how other approaches can be applied to enhance NK cell metabolism in tumors.<\/jats:p>","DOI":"10.1111\/imr.13316","type":"journal-article","created":{"date-parts":[[2024,3,9]],"date-time":"2024-03-09T08:24:57Z","timestamp":1709972697000},"page":"19-39","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Metabolic adaptations determine whether natural killer cells fail or thrive within the tumor microenvironment"],"prefix":"10.1111","volume":"323","author":[{"given":"Adnan","family":"Moinuddin","sequence":"first","affiliation":[{"name":"Department of Medicine McMaster University  Hamilton Ontario Canada"},{"name":"McMaster Immunology Research Centre McMaster University  Hamilton Ontario Canada"},{"name":"Centre for Discovery in Cancer Research McMaster University  Hamilton Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophie 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