STING agonism enhances anti-tumor immune responses and therapeutic efficacy of PARP inhibition in BRCA-associated breast cancer

被引：0

作者：

Constantia Pantelidou

Heta Jadhav

Aditi Kothari

Renyan Liu

Gerburg M. Wulf

Jennifer L. Guerriero

Geoffrey I. Shapiro

机构：

[1] Dana-Farber Cancer Institute,Department of Medical Oncology

[2] Beth Israel Deaconess Medical Center and Harvard Medical School,Department of Medicine, Division of Hematology

[3] Harvard Medical School,Oncology and Cancer Research Institute

[4] Dana-Farber Cancer Institute,Ludwig Center for Cancer Research at Harvard

[5] Brigham and Women’s Hospital,Breast Tumor Immunology Laboratory, Department of Cancer Biology

[6] Brigham and Women’s Hospital and Harvard Medical School,Division of Breast Surgery, Department of Surgery

[7] Bayer Pharmaceuticals,Department of Medicine

来源：

npj Breast Cancer | / 8卷

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摘要：

Poly (ADP-ribose) polymerase (PARP) inhibitors exert their efficacy via synthetic lethal effects and by inducing cGAS/STING-mediated immune responses. We demonstrate that compared to monotherapies, combined PARP inhibition and STING agonism results in increased STING pathway activation, greater cytotoxic T-cell recruitment and enhanced dendritic cell activation in BRCA1-deficient breast cancer models. The combination markedly improved anti-tumor efficacy in vivo, with evidence of complete tumor clearance, prolongation of survival and induction of immunologic memory.

引用

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[1] STING agonism enhances anti-tumor immune responses and therapeutic efficacy of PARP inhibition in BRCA-associated breast cancer
Pantelidou, Constantia
Jadhav, Heta
Kothari, Aditi
Liu, Renyan
Wulf, Gerburg M.
Guerriero, Jennifer L.
Shapiro, Geoffrey, I
NPJ BREAST CANCER, 2022, 8 (01)
[2] STING agonism enhances anti-tumor immune responses and therapeutic efficacy of PARP inhibition in BRCA-associated breast cancer
Jadhav, Heta
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[3] PARP inhibition modulates the infiltration, phenotype and function of tumor-associated macrophages (TAMs) in BRCA-associated breast cancer and can be augmented by harnessing the anti-tumor potential of TAMs
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[4] STING agonism reprograms tumor-associated macrophages and overcomes resistance to PARP inhibition in BRCA1-deficient models of breast cancer
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[9] Choosing wisely: Selecting PARP inhibitor combinations to promote anti-tumor immune responses beyond BRCA mutations
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[10] Overcoming immunosuppression and therapeutic resistance to PARP inhibition in BRCA1-deficient breast cancer with STING agonists.
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