Successful Anti-PD-1 Cancer Immunotherapy Requires T Cell-Dendritic Cell Crosstalk Involving the Cytokines IFN-? and IL-12 (Immunity)

Anti-PD-1 mAbs can induce sustained clinical responses in cancer but how they function in vivo remains incompletely understood. Garris et al. show that effective anti-PD-1 immunotherapy requires intratumoral dendritic cells (DCs) producing IL-12. Anti-PD-1 indirectly activates DCs through IFN-? released from drug-activated T cells. Furthermore, agonizing the non-canonical NF-?B pathway activates DCs and enhances aPD-1 therapy in an IL-12-dependent manner.