Significance Adjuvants enhance adaptive immune responses, sometimes through unknown mechanisms, and can be used to augment both humoral and cellular responses to cancer antigens. We report the immunological effects of the synthetic chemical adjuvant Diprovocim, which targets the innate immune receptor TLR1/TLR2 in mice and humans. Diprovocim displayed strong adjuvant activity in mice, particularly abetting cellular immune responses. Immunization against a genetically engineered tumor-specific antigen, ovalbumin, when adjuvanted with Diprovocim, inhibited growth of B16 melanoma and prolonged survival in the presence of immune checkpoint blockade by anti–PD-L1; 100% of mice responded to treatment. Our data suggest Diprovocim boosts the success of anti–PD-L1 treatment by increasing the number and activation of tumor-specific CTLs capable of responding to this checkpoint inhibitor.