{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T19:22:50Z","timestamp":1791400970516,"version":"4.3.3"},"reference-count":50,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2009,3,1]],"date-time":"2009-03-01T00:00:00Z","timestamp":1235865600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2009,3,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>V\u03b39V\u03b42 T lymphocytes are a major human \u03b3\u03b4 T cell subset that react against a wide array of tumor cells, through recognition of phosphorylated isoprenoid pathway metabolites called phosphoantigens. Immunotherapeutic protocols targeting V\u03b39V\u03b42 T cells have yielded promising, yet limited, signs of antitumor efficacy. To improve these approaches, we analyzed the effects on \u03b3\u03b4 T cells of IL-21, a cytokine known to enhance proliferation and effector functions of CD8+ T cells and NK cells. IL-21 induced limited division of phosphoantigen-stimulated V\u03b39V\u03b42 T cells, but did not modulate their sustained expansion induced by exogenous IL-2. V\u03b39V\u03b42 T cells expanded in the presence of IL-21 and IL-2 showed enhanced antitumor cytolytic responses, associated with increased expression of CD56 and several lytic molecules, and increased tumor-induced degranulation capacity. IL-21 plus IL-2-expanded V\u03b39V\u03b42 T cells expressed higher levels of inhibitory receptors (e.g., ILT2 and NKG2A) and lower levels of the costimulatory molecule NKG2D. Importantly, these changes were rapidly and reversibly induced after short-term culture with IL-21. Finally, IL-21 irreversibly enhanced the proinflammatory Th1 polarization of expanded V\u03b39V\u03b42 T cells when added at the beginning of the culture. These data suggest a new role played by IL-21 in the cytotoxic and Th1 programming of precommitted Ag-stimulated \u03b3\u03b4 T cells. On a more applied standpoint, IL-21 could be combined to IL-2 to enhance \u03b3\u03b4 T cell-mediated antitumor responses, and thus represents a promising way to optimize immunotherapies targeting this cell subset.<\/jats:p>","DOI":"10.4049\/jimmunol.0803068","type":"journal-article","created":{"date-parts":[[2009,3,5]],"date-time":"2009-03-05T20:01:20Z","timestamp":1236283280000},"page":"3423-3431","source":"Crossref","is-referenced-by-count":79,"title":["IL-21-Mediated Potentiation of Antitumor Cytolytic and Proinflammatory Responses of Human V\u03b39V\u03b42 T Cells for Adoptive Immunotherapy"],"prefix":"10.1093","volume":"182","author":[{"given":"Aur\u00e9lie","family":"Thedrez","sequence":"first","affiliation":[{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale, Unit\u00e9 892, Centre de Recherche en Canc\u00e9rologie Nantes-Angers , Nantes,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christelle","family":"Harly","sequence":"additional","affiliation":[{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale, Unit\u00e9 892, Centre de Recherche en Canc\u00e9rologie Nantes-Angers , Nantes,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexis","family":"Morice","sequence":"additional","affiliation":[{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale, Unit\u00e9 892, Centre de Recherche en Canc\u00e9rologie Nantes-Angers , Nantes,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuel","family":"Salot","sequence":"additional","affiliation":[{"name":"Innate Pharma , Marseille,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc","family":"Bonneville","sequence":"additional","affiliation":[{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale, Unit\u00e9 892, Centre de Recherche en Canc\u00e9rologie Nantes-Angers , Nantes,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emmanuel","family":"Scotet","sequence":"additional","affiliation":[{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale, Unit\u00e9 892, Centre de Recherche en Canc\u00e9rologie Nantes-Angers , Nantes,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2009,3,15]]},"reference":[{"key":"2026012807055236500_R1","first-page":"267","article-title":"Stimulation of human \u03b3\u03b4 T cells by nonpeptidic mycobacterial ligands.","volume-title":"Science","year":"1994"},{"key":"2026012807055236500_R2","first-page":"99","article-title":"The interplay between classical and alternative isoprenoid biosynthesis controls \u03b3\u03b4 T cell bioactivity of Listeria monocytogenes.","volume-title":"FEBS Lett.","year":"2004"},{"key":"2026012807055236500_R3","first-page":"503","article-title":"Sensing cell stress and transformation through V\u03b39V\u03b42 T cell-mediated recognition of the isoprenoid pathway metabolites.","volume-title":"Microbes Infect.","year":"2005"},{"key":"2026012807055236500_R4","first-page":"18337","article-title":"Chemical synthesis and biological activity of bromohydrin pyrophosphate, a potent stimulator of human \u03b3\u03b4 T cells.","volume-title":"J. 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