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This metabolic unfitness is closely associated with T\u2010cell exhaustion and impairment of memory formation, which are barriers to successful antitumor adoptive immunotherapy. We therefore assessed the role of glutamine metabolism in the antitumor activity of\n CD<\/jats:styled-content>\n 8\n +<\/jats:sup>\n T cells using a tumor\u2010inoculated mouse model. The adoptive transfer of tumor\u2010specific\n CD<\/jats:styled-content>\n 8\n +<\/jats:sup>\n T cells cultured under glutamine\u2010restricted (\n dG<\/jats:styled-content>\n ln) conditions or\n CD<\/jats:styled-content>\n 8\n +<\/jats:sup>\n T cells treated with specific inhibitors of glutamine metabolism efficiently eliminated tumors and led to better survival of tumor\u2010inoculated mice than with cells cultured under control (Ctrl) conditions. The decreased expression of\n PD<\/jats:styled-content>\n \u20101 and increased Ki67 positivity among tumor\u2010infiltrating\n CD<\/jats:styled-content>\n 8\n +<\/jats:sup>\n T cells cultured under\n dG<\/jats:styled-content>\n ln conditions suggested that the inhibition of glutamine metabolism prevents\n CD<\/jats:styled-content>\n 8\n +<\/jats:sup>\n T\u2010cell exhaustion in\u00a0vivo. Furthermore, the transferred\n CD<\/jats:styled-content>\n 8\n +<\/jats:sup>\n T cells cultured under\n dG<\/jats:styled-content>\n ln conditions expanded more efficiently against secondary\n OVA<\/jats:styled-content>\n stimulation than did\n CD<\/jats:styled-content>\n 8\n +<\/jats:sup>\n T cells under Ctrl conditions. We found that the expression of a pro\u2010survival factor and memory T cell\u2010related transcription factors was significantly higher in\n CD<\/jats:styled-content>\n 8\n +<\/jats:sup>\n T cells cultured under\n dG<\/jats:styled-content>\n ln conditions than in those cultured under Ctrl conditions. Given these findings, our study uncovered an important role of glutamine metabolism in the antitumor activity of\n CD<\/jats:styled-content>\n 8\n +<\/jats:sup>\n T cells. The novel adoptive transfer of tumor\u2010specific\n CD<\/jats:styled-content>\n 8\n +<\/jats:sup>\n T cells cultured in glutamine\u2010restricted conditions may be a promising approach to improve the efficacy of cell\u2010based adoptive immunotherapy.\n <\/jats:p>","DOI":"10.1111\/cas.13827","type":"journal-article","created":{"date-parts":[[2018,10,10]],"date-time":"2018-10-10T02:36:20Z","timestamp":1539138980000},"page":"3737-3750","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":178,"title":["Reinforce the antitumor activity of\n CD<\/scp>\n 8\n +<\/sup>\n T cells via glutamine restriction"],"prefix":"10.1111","volume":"109","author":[{"given":"Shogo","family":"Nabe","sequence":"first","affiliation":[{"name":"Department of Hematology, Clinical Immunology and Infectious Diseases Graduate School of Medicine Ehime University Toon 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