CCL5-Mediated Immune Interactions Drive Osteosarcoma Progression: Insights from Mendelian Randomization, Single-Cell...

Area of Science:

• Oncology
• Immunology
• Genetics

Background:

• Osteosarcoma is an aggressive bone cancer characterized by a complex immune microenvironment.
• Chronic inflammation and immune cell dysregulation are implicated in osteosarcoma progression, but causal links are unclear.

Purpose of the Study:

• To investigate the causal role of inflammatory cytokines and immune cells in osteosarcoma.
• To identify potential therapeutic targets by analyzing the immune landscape.

Main Methods:

• Integrated Mendelian Randomization (MR), single-cell RNA sequencing (scRNA-seq), and functional assays.
• MR identified causal associations between cytokines/immune traits and osteosarcoma risk.
• scRNA-seq and transcriptomic analysis profiled CCL5 expression and immune cell infiltration.

Main Results:

• CCL5 was identified as a pro-tumorigenic cytokine causally linked to osteosarcoma.
• Monocytes, macrophages, and fibroblasts were identified as major CCL5 producers.
• CCL5 expression correlated with increased infiltration of specific immune cells (Tregs, M1 macrophages) and advanced tumor stage.

Conclusions:

• CCL5 plays a critical role in shaping the osteosarcoma immune microenvironment and promoting tumor growth.
• CCL5 is a potential biomarker and immunotherapeutic target for osteosarcoma.
• Understanding CCL5's role provides mechanistic insights into osteosarcoma pathogenesis.