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

期刊

SCIENCE IMMUNOLOGY
卷 6, 期 65, 页码 -

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AMER ASSOC ADVANCEMENT SCIENCE

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资金

  1. National Institute of General Medical Sciences [T32GM007753]
  2. NIH [P01 AI56299, P01AI039671, P01 AI108545, P01 AI073748, U24 AI11867, R01 AI22220, UM 1HG009390, P01 AI039671, P50 CA121974, R01 CA227473]

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Immune checkpoint blockade has shown success in cancer treatment but can result in immune-related adverse events. The control of T cell responses by programmed cell death protein 1 (PD-1) is discussed, with a focus on its specific restraint of regulatory T cell function. Strategies to modulate PD-1 blockade to enhance anti-tumor immunity while limiting autoimmunity are reviewed.
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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