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Lactate dehydrogenase inhibition synergizes with IL-21 to promote CD8+T cell stemness and antitumor immunity

Hermans, Dalton ; Gautam, Sanjivan ; García-Cañaveras, Juan C. ; Gromer, Daniel ; Mitra, Suman ; Spolski, Rosanne ; Li, Peng ; Christensen, Stephen ; Nguyen, Rosa ; Lin, Jian-Xin ; Oh, Jangsuk ; Du, Ning ; Veenbergen, Sharon ; Fioravanti, Jessica ; Ebina-Shibuya, Risa ; Bleck, Christopher ; Neckers, Leonard M. ; Rabinowitz, Joshua D. ; Gattinoni, Luca ; Leonard, Warren J.


Interleukin (IL)-2 and IL-21 dichotomously shape CD8(+) T cell differentiation. IL-2 drives terminal differentiation, generating cells that are poorly effective against tumors, whereas IL-21 promotes stem cell memory T cells (T-SCM) and antitumor responses. Here we investigated the role of metabolic programming in the developmental differences induced by these cytokines. IL-2 promoted ...


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