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

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Chemokine ligand 5 (CCL5) drives osteosarcoma progression by influencing immune cells. Targeting CCL5 may offer new therapeutic strategies for this aggressive bone cancer.

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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.