Pan-cancer bone metastasis atlas at single-cell resolution identifies a distinct tumor-associated macrophage subset for mediating Denosumab-induced immunosensitization in lung cancer bone metastasis.

ABSTRACT: Lung cancer (LC), prostate cancer (PC), and breast cancer (BC) are the three most prevalent cancers that lead to bone metastasis (BoM). In this study, we conducted an integrated analysis of single-cell transcriptomic data from the primary tumors and BoM across PC, LC, and BC. We discover a novel subtype of tumor-associated macrophages (TAMs) that are positive both for matrix metalloproteinase 19 (MMP19) and receptor activator of nuclear factor-κB (RANK) expression (MMP19⁺ RANK⁺ TAMs). MMP19⁺ RANK⁺ TAMs demonstrate an increased level of M2 polarization and act as a critical driving factor for LC-BoM. MMP19⁺ RANK⁺ TAMs are organized in a ring-like arrangement surrounding the tumor nests, constructing a barrier structure that i

SUBMITTER: Hu X 

PROVIDER: S-EPMC12681936 | biostudies-literature | 2026

REPOSITORIES: biostudies-literature