articleNature CommunicationsFeb 17, 2016GOLD OA

Adaptive resistance to therapeutic PD-1 blockade is associated with upregulation of alternative immune checkpoints

SKShohei KoyamaEAEsra A. AkbayYYYvonne Y. LiGSGrit S. Herter-SprieKAKevin A. Buczkowski

Brigham and Women's Hospital · Dana-Farber Cancer Institute · +7 more institutions

PubMed
Indexed incrossrefdoajpubmed

Abstract

Despite compelling antitumour activity of antibodies targeting the programmed death 1 (PD-1): programmed death ligand 1 (PD-L1) immune checkpoint in lung cancer, resistance to these therapies has increasingly been observed. In this study, to elucidate mechanisms of adaptive resistance, we analyse the tumour immune microenvironment in the context of anti-PD-1 therapy in two fully immunocompetent mouse models of lung adenocarcinoma. In tumours progressing following response to anti-PD-1 therapy, we observe upregulation of alternative immune checkpoints, notably T-cell immunoglobulin mucin-3 (TIM-3), in PD-1 antibody bound T cells and demonstrate a survival advantage with addition of a TIM-3 blocking antibody…

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Topics & keywords

Topics
Keywords
  • Downregulation and upregulation
  • Blockade
  • Immune system
  • Immune checkpoint
  • PD-L1
  • Antibody
  • Acquired immune system
  • Blocking antibody
UN Sustainable Development Goals
  • Good health and well-being
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