Targeting HSP90 sensitizes pancreas carcinoma to PD-1 blockade

Interferon gamma (IFNG/IFN gamma)-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 IFN gamma-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.

Automated summary

In this study, it was found that the chaperone protein HSP90 stabilizes STAT1, which leads to the expression of immunosuppressive factors IDO1 and PD-L1 induced by IFN gamma. Pharmacological inhibition of HSP90 enhances the efficacy of PD-1 immunotherapy in suitable mouse models without any toxicity.