Targeting HSP90 sensitizes pancreas carcinoma to PD-1 blockade

Jiao Liu; Rui Kang; Guido Kroemer; Daolin Tang

doi:10.1080/2162402X.2022.2068488

Targeting HSP90 sensitizes pancreas carcinoma to PD-1 blockade

Jiao Liu, Rui Kang, Guido Kroemer, Daolin Tang

Research output: Contribution to journal › Article › peer-review

6 Citations (Scopus)

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
Article number	2068488
Journal	OncoImmunology
Volume	11
Issue number	1
DOIs	https://doi.org/10.1080/2162402X.2022.2068488
Publication status	Published - 1 Jan 2022

Keywords

Adaptive immune resistance
immune checkpoint
molecular chaperone
pancreatic cancer
protein degradation

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10.1080/2162402X.2022.2068488

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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.",

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AU - Kang, Rui

AU - Kroemer, Guido

AU - Tang, Daolin

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AB - 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.

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Targeting HSP90 sensitizes pancreas carcinoma to PD-1 blockade

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