Background: The immune system conditions of patients with osteosarcoma correlate with the neoadjuvant therapy administration. NK cell (natural killer cell) of macrophages are known as proinflammatory macrophages (macrophage-1/M-1). If IFN-γ decreases, NK cells will be inactivated so that they cannot destroy cancer cells. This condition occurs due to the activities of anti-inflammatory macrophages, known as macrophage-2 (M-2). Purpose: This study aims to determine the correlation between M-1 and M-2 in patients with osteosarcoma, ranging from non-metastatic to metastatic osteosarcoma. Method: There were 26 patients with osteosarcoma, consisting of 13 samples with stage IIB osteosarcoma and 13 samples with stage III osteosarcoma. TNF-α and IL-10, which became intermediate variables for the M1/M2 ratio, were immunohistochemically stained and counted in 10 visual fields (visual field: 15625μ²) with 400 times magnification. The data analysis was performed using a statistical test, i.e., difference test using the Mann-Whitney U test between groups of patients with stage IIB and stage III osteosarcoma on IL-10 and TNF-α. Results: M1/M2 ratio on osteosarcoma, in terms of anti-inflammatory aspect, i.e., based on the number of macrophages that express IL-10 between patients with stage IIB and stage III osteosarcoma, reached 1:6.4, rounded to 1:6. Meanwhile, the M1/M2 ratio on osteosarcoma in terms of proinflammatory aspect amounted to 5:1. Conclusion: The result of the M1/M2 ratio on stage IIB osteosarcoma tissue is five times greater on M-1 macrophages, while the M1/M2 ratio on stage III osteosarcoma is six times greater on M-2 macrophages.

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