Targeting HSP90 sensitizes pancreas carcinoma to PD-1 blockade

Review Immunology

Immunogenic cell stress and death

Guido Kroemer et al.

Summary: Immunogenic cell death (ICD) plays an important role in therapy and disease, as dying mammalian cells release signals that interact with the host to determine the immunological correlates of cellular stress and death. ICD is crucial in immunosurveillance and is related to strategies evolved by pathogens and cancer cells. Additionally, normal cell death can also initiate antigen-specific immune responses.

NATURE IMMUNOLOGY (2022)

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Article Oncology

HSP90 Mediates IFNγ-Induced Adaptive Resistance to Anti-PD-1 Immunotherapy

Ke Liu et al.

Summary: This study uncovers the HSP90-centric, iron-modulated mechanism that confers immunosuppression, potentially providing therapeutic targets for overcoming acquired resistance to anticancer immunotherapies. The upregulation of immune checkpoints induced by IFN gamma requires increased protein stability of STAT1, mediated by the HSP90-SUGT1 chaperone complex. In addition, the upregulation of IDO1 in cancer cells acts as an immunosuppressive feedback mechanism. Combination therapies involving anti-PD-1 immunotherapy, iron chelation, HSP90 inhibition, or IDO1 inhibition show effectiveness and safety in preclinical models of pancreatic cancer.

CANCER RESEARCH (2022)

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Review Immunology

Interferon-γ: teammate or opponent in the tumour microenvironment?

Angela M. Gocher et al.

Summary: IFN gamma plays pleiotropic roles in the tumor microenvironment, acting as both a 'teammate' to promote antitumor immune responses and an 'opponent' promoting tumor growth and suppressing immune responses.

NATURE REVIEWS IMMUNOLOGY (2022)

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Article Gastroenterology & Hepatology

CDK1/2/5 inhibition overcomes IFNG-mediated adaptive immune resistance in pancreatic cancer

Jin Huang et al.

Summary: Inhibition of CDK1/2/5 kinase activity can overcome IFNG-mediated immune evasion in pancreatic tumors, turning a 'cold' tumor microenvironment into a 'hot' one and significantly improving overall survival rates in mouse pancreatic tumor models. Abnormal expression of CDK1/2/5 and IDO1 is associated with poor patient survival in various cancer types, including PDAC.

GUT (2021)

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Review Oncology