Systematic Review of Macrophage Polarization in Osteosarcoma Immunotherapy

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Frontiers in Medicine Published May 25, 2026 Medically reviewed May 25, 2026 DOI ↗ By Dr. Amelia Tan, PhD · Internal Medicine & Chronic Disease

Key Takeaway

Consider that macrophage polarization targeting remains preclinical; clinical applicability is not yet established.

This systematic review examines the potential of targeting and regulating macrophage polarization as a therapeutic strategy in osteosarcoma. The authors synthesize preclinical evidence indicating that manipulating macrophage phenotypes could influence tumor progression and immune response. The review provides a theoretical framework and strategic references for developing precise immunotherapy in osteosarcoma.

Key findings are derived from preclinical studies, as no clinical trials were included. The review does not report pooled effect sizes or quantitative outcomes, reflecting the early stage of this research area. The authors highlight that macrophage polarization may be a promising target, but evidence is limited to experimental models.

Limitations include the absence of clinical data, lack of reported sample sizes, and no comparator interventions. The review does not address safety or adverse events, as these were not reported in the included studies. The certainty of the evidence is not assessed.

For clinicians, this review offers conceptual insights but does not provide actionable clinical recommendations. The findings underscore the need for further translational research before macrophage polarization modulation can be considered in osteosarcoma treatment.

Study Details

Study typeMeta analysis

EvidenceLevel 1

PublishedMay 2026

View Original Abstract ↓

Osteosarcoma is the most common type of primary malignant bone tumour in children and adolescents. Despite advances in surgery and neoadjuvant chemotherapy, tumour metastasis and recurrence are still the main factors affecting patient prognosis. Recent research has shown that immune cells in the tumour microenvironment (TME), particularly tumour-associated macrophages (TAMs), play a crucial role in osteosarcoma progression. Macrophages exhibit high plasticity and can differentiate into the M1 type, which has anti-tumour functions, or the M2 type, which promotes tumour development. This paper provides a systematic review of the research on TAMs and their mechanisms in promoting osteosarcoma progression by driving tumour cell proliferation, mediating immune evasion and facilitating metastasis and angiogenesis. Additionally, it provides a systematic outline of potential therapeutic strategies for inhibiting osteosarcoma development by targeting and regulating macrophage polarisation. These strategies include drug interventions, nanotechnology and combined immunotherapy. This paper aims to elucidate the key mechanisms by which macrophage polarisation regulates the biological behaviour of osteosarcoma. This will provide a theoretical basis and strategic references for the precise immunotherapy of osteosarcoma.