Research ArticleIMMUNOTHERAPY

PD-1 blockade exacerbates Mycobacterium tuberculosis infection in rhesus macaques

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Science Immunology  15 Jan 2021:
Vol. 6, Issue 55, eabf3861
DOI: 10.1126/sciimmunol.abf3861

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PD-1 blockade carries perils

The potentiation of T cell–mediated antitumor responses achieved in multiple types of cancer via inhibition of the 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 patients with cancer with a history of Mtb exposure.

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