Cytotoxic CD4+ circulate between the blood and tumor of bladder cancer patients, where they exist as clonally related but distinct pools of granzyme B+ effector cells dually inhibited by PD-1 and KLRG1, and effector memory granzyme K+ cells that are not mobilized by PD-1 blockade. The gene discussed is PDCD1; the disease is urinary bladder cancer.