CCL5-Mediated Immune Interactions Drive Osteosarcoma Progression: Insights from Mendelian Randomization, Single-Cell Analysis, and Functional Validation - PubMed
6 hours ago
- #CCL5
- #immune microenvironment
- #osteosarcoma
- CCL5 is identified as a pro-tumorigenic cytokine with a significant causal association with osteosarcoma (OR > 15).
- Monocytes/macrophages and fibroblasts are the major CCL5-producing cells in osteosarcoma.
- Four immune traits are causally linked to osteosarcoma: CD86 expression on monocytes and CD127 expression on CD4+ T cells (risk factors), and CD8dim T cell and terminally differentiated CD4+ T cell counts (protective factors).
- CCL5 expression positively correlates with infiltration of CD8+ T cells, Tregs, and M1 macrophages, and is associated with advanced tumor stage.
- Tumor-associated macrophages with high CCL5 expression enhance osteosarcoma cell proliferation and colony formation.
- CCL5 plays a central role in shaping the immune landscape of osteosarcoma and promoting tumor progression, making it a promising biomarker and immunotherapeutic target.