Targeting HSP90 sensitizes pancreas carcinoma to PD-1 blockade

Jiao Liu, Rui Kang, Guido Kroemer, Daolin Tang

Research output: Contribution to journalArticlepeer-review

Abstract

Interferon gamma (IFNG/IFNγ)-induced adaptive immune resistance remains a challenge for tumor therapy. We observed that the chaperone heat shock protein 90 (HSP90) stabilizes the transcription factor signal transducer and activator of transcription 1 (STAT1), resulting in IFNγ-induced expression of immunosuppressive indoleamine 2,3-dioxygenase 1 (IDO1) and programmed death-ligand 1 (PD-L1/CD274). Pharmacological inhibition of HSP90 enhances the efficacy of programmed cell death 1 (PDCD1/PD-1) targeting immunotherapy in suitable mouse models without any toxicity.

Original languageEnglish (US)
Article number2068488
JournalOncoImmunology
Volume11
Issue number1
DOIs
StatePublished - 2022

Keywords

  • Adaptive immune resistance
  • immune checkpoint
  • molecular chaperone
  • pancreatic cancer
  • protein degradation

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Oncology

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