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 language | English (US) |
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Article number | 2068488 |
Journal | OncoImmunology |
Volume | 11 |
Issue number | 1 |
DOIs | |
State | Published - 2022 |
Keywords
- Adaptive immune resistance
- immune checkpoint
- molecular chaperone
- pancreatic cancer
- protein degradation
ASJC Scopus subject areas
- Immunology and Allergy
- Immunology
- Oncology