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Review
. 2021 Nov 5;6(65):eabf4034.
doi: 10.1126/sciimmunol.abf4034. Epub 2021 Nov 5.

The double-edged sword: Harnessing PD-1 blockade in tumor and autoimmunity

Juhi R Kuchroo  1   2 , David A Hafler  3   4 , Arlene H Sharpe  1   2   4   5 , Liliana E Lucca  3
Affiliations
Review

The double-edged sword: Harnessing PD-1 blockade in tumor and autoimmunity

Juhi R Kuchroo et al. Sci Immunol. .

Abstract

Immune checkpoint blockade has demonstrated success in treating cancer but can lead to immune-related adverse events (irAEs), illustrating the centrality of these pathways in tolerance. Here, we describe programmed cell death protein 1 (PD-1) control of T cell responses, focusing on its unique restraint of regulatory T cell function. We examine successes and limitations of checkpoint blockade immunotherapy and review clinical and mechanistic features of irAEs. Last, we discuss strategies to modulate PD-1 blockade to enhance antitumor immunity while limiting autoimmunity.

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