OX40 is a potent immune stimulating target. Provided herein is a method of treating cancer, which includes administering to a subject in need of treatment an OX40 agonist and a common gamma chain (yc) cytokine or an active fragment, variant, analog, or derivative thereof. In certain aspects the common gamma chain (yc) cytokine is interleukin-2 (IL-2) or an active fragment, variant, analog, or derivative thereof. Combined treatment with an agonist anti-OX40 mAb and IL-2 synergized to augment tumor immunotherapy against multiple tumor types. Dual therapy was also able to restore the function of anergic tumor-reactive CD8+ T cells.
