BU-BMC Cancer Center, Boston University School of Medicine, Boston, MA, USA; Institut Necker-Enfants Malades (INEM), Institut National de Recherche Médicale (INSERM) U1151, Laboratory of Onco-Hematology, Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Necker Enfants-Malades, Université de Paris, Paris, France.
BU-BMC Cancer Center, Boston University School of Medicine, Boston, MA, USA.
Cancer Lett. 2019 Nov 28;465:45-58. doi: 10.1016/j.canlet.2019.08.013. Epub 2019 Aug 29.
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.
旨在利用抗肿瘤免疫的治疗策略正在被深入研究，因为它们在癌症治疗中显示出了有前景的结果。PD-1/PD-L1 通路是恢复功能性抗肿瘤免疫反应的一个重要靶点。在这里，我们报告 BET 蛋白抑制可抑制三阴性乳腺癌中的 PD-1/PD-L1。BET 蛋白控制 T 细胞中的 PD-1 表达，以及乳腺癌细胞模型中的 PD-L1。BET 蛋白靶向可减少 T 细胞衍生的干扰素-γ产生和信号传导，从而抑制乳腺癌细胞中 PD-L1 的诱导。此外，BET 蛋白抑制可改善肿瘤细胞特异性 T 细胞的细胞毒性功能。总的来说，我们证明了 BET 蛋白靶向通过降低三阴性乳腺癌中的 PD-1/PD-L1 轴，代表了克服肿瘤反应性 T 细胞耗竭和增强抗肿瘤免疫反应的一种有前途的策略。
