Compositions and methods for enhancing an immune response and treating cancer are provided. Compositions comprise PD-1 axis antagonists and HPK1 antagonists. PD-1 axis antagonists include PD-1 antagonists, PD-L1 antagonists, and PD-L2 antagonists. PD-1 axis antagonists can inhibit the binding of PD-L1 and/or PD-L2 to PD-1. HPK1 antagonists include compounds that inhibit the serine/threonine kinase activity of HPK1. Methods for enhancing an immune response or treating cancer comprise administering a PD-1 axis antagonist and a HPK1 antagonist, sequentially or simultaneously, to a subject in need thereof.
