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These functions are triggered upon T-cell receptor\u2013dependent activation by non-peptidic prenyl pyrophosphates (\u201cphosphoantigens\u201d) that are selective agonists of V\u03b39V\u03b42 T cells, and which have been evaluated in clinical studies. Because phosphoantigens have shown interindividual variation in V\u03b39V\u03b42 T-cell activities, we asked whether metabolic resources, namely lipids such as cholesterol, could affect phosphoantigen-mediated V\u03b39V\u03b42 T-cell activation and function. We show here that V\u03b39V\u03b42 T cells express the LDL receptor upon activation and take up LDL cholesterol. Resulting changes, such as decreased mitochondrial mass and reduced ATP production, correlate with downregulation of V\u03b39V\u03b42 T-cell activation and functionality. In particular, the expression of IFN\u03b3, NKG2D, and DNAM-1 were reduced upon LDL cholesterol treatment of phosphoantigen-expanded V\u03b39V\u03b42 T cells. As a result, their capacity to target breast cancer cells was compromised both in vitro and in an in vivo xenograft mouse model. Thus, this study describes the role of LDL cholesterol as an inhibitor of the antitumor functions of phosphoantigen-activated V\u03b39V\u03b42 T cells. Our observations have implications for therapeutic applications dependent on V\u03b39V\u03b42 T cells. Cancer Immunol Res; 6(4); 448\u201357. \u00a92018 AACR.<\/jats:p>","DOI":"10.1158\/2326-6066.cir-17-0327","type":"journal-article","created":{"date-parts":[[2018,1,22]],"date-time":"2018-01-22T20:20:10Z","timestamp":1516652410000},"page":"448-457","update-policy":"https:\/\/doi.org\/10.1158\/crossmark_policy","source":"Crossref","is-referenced-by-count":38,"title":["Low-Density Lipoprotein Uptake Inhibits the Activation and Antitumor Functions of Human V\u03b39V\u03b42 T Cells"],"prefix":"10.1158","volume":"6","author":[{"given":"Neidy V.","family":"Rodrigues","sequence":"first","affiliation":[{"name":"1Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Portugal."},{"name":"2Instituto Gulbenkian de Ci\u00eancia, Oeiras, Portugal."},{"name":"3Programa de P\u00f3s-Gradua\u00e7\u00e3o Ci\u00eancia para o Desenvolvimento, Oeiras, Portugal."},{"name":"4Faculdade de Ci\u00eancia e Tecnologia, Uni-CV, Campus do Palmarejo, Praia, Cabo Verde."}]},{"given":"Daniel 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