BET Protein Targeting Suppresses the PD-1/PD-L1 Pathway in Triple-negative Breast Cancer and Elicits Anti-tumor Immune Response

Overview

Journal Cancer Lett

Specialty Oncology

Date 2019 Sep 2

PMID 31473251

Citations 23

Authors

Guillaume P Andrieu

Jordan S Shafran

Charlotte L Smith

Anna C Belkina

Allison N Casey

Naser Jafari

Gerald V Denis

Affiliations

Soon will be listed here.

Abstract

Therapeutic strategies aiming to leverage anti-tumor immunity are being intensively investigated as they show promising results in cancer therapy. The PD-1/PD-L1 pathway constitutes an important target to restore functional anti-tumor immune response. Here, we report that BET protein inhibition suppresses PD-1/PD-L1 in triple-negative breast cancer. BET proteins control PD-1 expression in T cells, and PD-L1 in breast cancer cell models. BET protein targeting reduces T cell-derived interferon-γ production and signaling, thereby suppressing PD-L1 induction in breast cancer cells. Moreover, BET protein inhibition improves tumor cell-specific T cell cytotoxic function. Overall, we demonstrate that BET protein targeting represents a promising strategy to overcome tumor-reactive T cell exhaustion and improve anti-tumor immune responses, by reducing the PD-1/PD-L1 axis in triple-negative breast cancer.

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