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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.