Osteoclast-derived apoptotic bodies inhibit naive CD8⁺ T cell activation via Siglec15, promoting breast cancer secondary metastasis.

ABSTRACT: 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 ant

SUBMITTER: Wu Y 

PROVIDER: S-EPMC10518580 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature