Abstract
Cancer Immunology Immune checkpoint–inhibitor therapies bolster the antitumor activity of CD8+ T lymphocytes. Wang et al. performed single-cell analysis of tumor-infiltrating lymphocytes in mouse cancer models in which inhibitory anti–PD-1 (programmed cell death protein 1) and stimulatory anti–GITR (glucocorticoid-induced tumor necrosis factor receptor–related protein) antibodies together enhanced tumor control. This combination immunotherapy led to a synergistic increase in tumor antigen–specific memory precursor effector T cells dependent on the CD226 costimulatory pathway. Biochemical studies in liposomes identified CD226 as an additional target of dephosphorylation mediated by the PD-1–SHP2 (Src homology region 2) complex. Thus, further clinical trials could usefully test the efficacy of combined anti-GITR and anti–PD-1 immunotherapy in human cancer. Sci. Immunol. 3 , eaat7061 (2018).
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