A method of treating a subject can include administering to a subject in need thereof an effective amount of a killer cell lectin-like receptor G1 (KLRG1)/ligand binding agent, thereby disrupting KLRG1 signaling and activating CD8+ cytotoxic T and/or NK cells. A method of treating cancer can include administering to a subject in need thereof an effective amount of a killer cell lectin-like receptor G1 (KLRG1)/ligand binding agent. The methods can treat various cancers, for example melanoma, lung cancer, pancreatic cancer, glioma, breast cancer, and ovarian cancer.
