Microparticles (MPs) are a heterogeneous subpopulation of extracellular vesicles that originate from the plasma membranes of cells. There is increasing evidence that tumor-derived MPs (T-MPs) play a significant role in tumor progression and immune response in cancer. In our study, we found an increased secretion of MPs in osteosarcoma tissues obtained from metastatic patients. These T-MPs promoted polarization of M2-like macrophages and stimulated the migration and chemoresistance of osteosarcoma cells. Mechanistically, T-MPs promoted macrophage polarization to an M2-like phenotype through TBK1-STAT6 signaling. Consequently, these M2-like macrophages mediated osteosarcoma cell migration via CCL18/STAT3 signaling. Blockade of STAT3 signaling pathway improved the outcome of chemotherapy in LM8-bearing osteosarcoma mice model. Thus, our study reveals how tumor cells regulate macrophage polarization by releasing MPs and provides new insights into clinical osteosarcoma therapy.

微粒（MP）是源自细胞质膜的细胞外囊泡的异质亚群。越来越多的证据表明，肿瘤源性 MP (T-MP) 在肿瘤进展和癌症免疫反应中发挥着重要作用。在我们的研究中，我们发现从转移性患者获得的骨肉瘤组织中 MP 的分泌增加。这些 T-MP 促进 M2 样巨噬细胞的极化，刺激骨肉瘤细胞的迁移和化疗耐药。从机制上讲，T-MP 通过 TBK1-STAT6 信号传导促进巨噬细胞极化为 M2 样表型。因此，这些 M2 样巨噬细胞通过 CCL18/STAT3 信号传导介导骨肉瘤细胞迁移。阻断 STAT3信号通路可改善携带 LM8 的骨肉瘤小鼠模型的化疗效果。因此，我们的研究揭示了肿瘤细胞如何通过释放MP来调节巨噬细胞极化，并为临床骨肉瘤治疗提供了新的见解。