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2 The immunotherapeutic landscape of osteosarcoma: challenges and resistance mechanisms 2.1 The immunosuppressive TME The osteosarcoma TME is a complex ecosystem comprising malignant cells, stromal cells, immune infiltrates, and ECM components embedded within a mineralized bone scaffold ( TAMs represent the most abundant immune cell population within the osteosarcoma TME, often accounting for over 50% of infiltrating immune cells (30)

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Moreover, the osteocyte-specific knockout of igf-1 , displays a 59% reduction of IGF-1 mRNA levels in skeletal muscle, although gross muscle architecture appeared normal (Sheng et al., 2013)

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