文章：

抑制髓系PD-L1抑制破骨细胞发生和癌症骨转移

Inhibition of myeloid PD-L1 suppresses osteoclastogenesis and cancer bone metastasis 

原文发布日期：2022-03-07 

英文摘要：

Programmed death-ligand 1 (PD-L1) is predominantly expressed in the antigen-presenting cells (APCs) that are originated and are abundant in the bone marrow. The roles of PD-L1 in bone cell differentiation and cancer bone metastasis remain unclear. Here we show that PD-L1 antibody or PD-L1 conditional knockout in the hematopoietic or myeloid lineage suppresses osteoclast differentiation in vitro and in vivo. Bone metastases of breast cancer and melanoma are diminished by PD-L1 antibody or PD-L1 deletion in the myeloid lineage. Transcriptional profiling of bone marrow cells reveals that PD-L1 deletion in the myeloid cells upregulates immune-stimulatory genes, leading to increased macrophage M1 polarization, decreased M2 polarization, enhanced IFNγ signaling, and elevated T cell recruitment and activation. All these alterations result in heightened anti-tumor immunity in the cancer microenvironment. Our findings support PD-L1 antibody as a potent therapy for bone metastasis of breast cancer and melanoma by simultaneously suppressing osteoclast and enhancing immunity. 

摘要翻译： 

程序性死亡配体1（PD-L1）主要表达于源自骨髓且大量存在于骨髓中的抗原呈递细胞（APCs）。PD-L1在骨细胞分化和癌症骨转移中的作用尚不明确。本研究显示，在造血系统或髓系细胞中使用PD-L1抗体或条件性敲除PD-L1，可在体外和体内抑制破骨细胞分化。通过PD-L1抗体或髓系细胞PD-L1缺失，乳腺癌和黑色素瘤的骨转移得到抑制。骨髓细胞转录组分析表明，髓系细胞PD-L1缺失可上调免疫刺激基因，导致巨噬细胞M1极化增强、M2极化减弱，IFNγ信号通路激活，T细胞招募和活化增加。这些变化共同增强了肿瘤微环境中的抗肿瘤免疫。我们的研究结果支持PD-L1抗体通过同时抑制破骨细胞和增强免疫，成为治疗乳腺癌和黑色素瘤骨转移的有效疗法。

原文链接：

Inhibition of myeloid PD-L1 suppresses osteoclastogenesis and cancer bone metastasis