骨骼微环境促进癌细胞的增殖和传播。在骨周期性重塑期间，破骨细胞经历凋亡，产生大量凋亡小体（ABs）。然而，作为骨肿瘤微环境常驻细胞的破骨细胞源性AB的生物学作用仍然很大程度上未知。在这里，我们发现AB缺失的MRL/lpr小鼠对乳腺癌细胞植入显示出抗性，具有更多CD8+ T细胞浸润和更高的存活率。我们发现破骨细胞源性AB上的膜结合受体标志蛋白15（Siglec15）与唾液酸化的Toll样受体2（TLR2）结合并阻断下游共刺激信号传导，从而抑制原始CD8+ T细胞的活化。此外，我们的研究表明，Siglec15中和抗体处理显著降低了次级转移的发生率，提高了具有晚期乳腺癌骨转移的小鼠的存活率。我们的发现揭示了破骨细胞源性AB在骨肿瘤微环境中的免疫抑制功能，并展示了Siglec15作为抗吸收和免疫疗法的常见靶点的潜力。版权©2023年作者。Elsevier Inc.发表，版权所有。

The bone microenvironment promotes cancer cell proliferation and dissemination. During periodic bone remodeling, osteoclasts undergo apoptosis, producing large numbers of apoptotic bodies (ABs). However, the biological role of osteoclast-derived ABs, which are residents of the bone-tumor niche, remains largely unknown. Here, we discover that AB-null MRL/lpr mice show resistance to breast cancer cell implantation, with more CD8+ T cell infiltrations and a higher survival rate. We uncover that the membranous Siglec15 on osteoclast-derived ABs binds with sialylated Toll-like receptor 2 (TLR2) and blocks downstream co-stimulatory signaling, leading to the inhibition of naive CD8+ T cell activation. In addition, our study shows that treatment with Siglec15 neutralizing antibodies significantly reduces the incidence of secondary metastases and improves the survival rate of mice with advanced breast cancer bone metastasis. Our findings reveal the immunosuppressive function of osteoclast-derived ABs in the bone-tumor niche and demonstrate the potential of Siglec15 as a common target for anti-resorption and immunotherapy.Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.