Immunotherapy with a sting

New agonists of an innate immune pathway induce antitumor immunity in mice Tumor antigen-specific CD8+ T cells are a critical component of the antitumor immune response. Many cancer patients display evidence of an endogenous T cell response against their tumors, yet fail to eliminate tumors unaided. The failure of spontaneous immune-mediated tumor rejection is thought to be partially due to the action of negative regulatory mechanisms (immune checkpoints) that inhibit key functional properties of tumor-infiltrating T cells (1). Checkpoint blockade immunotherapies have demonstrated notable therapeutic success by overcoming tumor-induced T cell inhibition; however, their efficacy is poor when patients lack evidence of a spontaneous T cell response (2, 3). Innate immune agonists may promote priming and recruitment of tumor-specific CD8+ T cells and are gaining traction as a cancer immunotherapy approach. On page 935 and 993 of this issue, Pan et al. (4) and Chin et al. (5), respectively, describe innate immune agonists that show antitumor activity in preclinical cancer models.