PD-1 blockade carries perils

Abstract

Immunotherapy The potentiation of T cell–mediated antitumor responses achieved in multiple types of cancer through inhibition of the programmed death-1 (PD-1) checkpoint pathway has led to suggestions that anti–PD-1 therapy might also boost T cell immunity in chronic infections, including tuberculosis. Kauffman et al. examined the effect of anti–PD-1 antibody treatment on the clinical course of Mycobacterium tuberculosis (Mtb) infection in rhesus macaques. CD8 T cell responses were boosted in monkeys receiving anti–PD-1 infusions, but the stronger CD8 T cell responses were coupled with increases in proinflammatory cytokines, impaired CD4 T cell function, and higher bacterial loads in lung granulomas. These findings in a nonhuman primate model signal that anti–PD-1–based therapy needs to be used cautiously in cancer patients with a history of Mtb exposure. Sci. Immunol. 6 , eabf3861 (2021).