The present disclosure describes combination therapies comprising an antagonist of Programmed Death 1 receptor (PD-1) and an antagonist of IL-27, and the use of the combination therapies for the treatment of cancer. In certain embodiments, the PD-1 antagonist is an anti-human PD-1 antibody, or antigen binding fragment thereof. In further embodiments, the anti-PD-1 antibody is pembrolizumab. In certain embodiments the antagonist of IL-27 is an anti-IL-27 antibody, or antigen binding fragment thereof, an anti-p28 antibody, or antigen binding fragment thereof, or an anti-EBI-3 antibody, or antigen binding fragment thereof. Also provided are medicaments, compositions, and kits comprising a PD-1 antagonist and an IL-27 antagonist for use in treating cancer.