The immunity analysis on osteosarcoma as the basic development of therapy follow-up


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.


  • Abbas, A., Andrew, H., Shiv, P.(2010). Cellular and Molecular Immunology. 6th ed. Saunders Elsevier; pp. 257-318.
  • Abdurachman, A., & Herawati, N. (2018). The role of psychological well-being in boosting immune response: an optimal effort for tackling infection. African journal of infectious diseases, 12(1S), 54-61.
  • Chuang, Y., Hung, M. E., Cangelose, B. K., & Leonard, J. N. (2016). Regulation of the IL-10-driven macrophage phenotype under incoherent stimuli. Innate immunity, 22(8), 647-657.
  • Deavall, D. G., Martin, E. A., Horner, J. M., & Roberts, R. (2012). Drug-induced oxidative stress and toxicity. Journal of toxicology, 2012.
  • Kurahara, H., Shinchi, H., Mataki, Y., Maemura, K., Noma, H., Kubo, F., ... & Takao, S. (2011). Significance of M2-polarized tumor-associated macrophage in pancreatic cancer. Journal of Surgical Research, 167(2), e211-e219.
  • Shih, J. Y., Yuan, A., Chen, J. J. W., & Yang, P. C. (2006). Tumor-associated macrophage: its role in cancer invasion and metastasis. J Cancer Mol, 2(3), 101-106.
  • Sica, A., Schioppa, T., Mantovani, A., & Allavena, P. (2006). Tumour-associated macrophages are a distinct M2 polarised population promoting tumour progression: potential targets of anti-cancer therapy. European journal of cancer, 42(6), 717-727.
  • Sorbi, A., & Farrokhnia, A. (2018). Landslide Hazard Evaluation and Zonation of Karaj-Chalus Road (North of Iran). International Journal of Geography and Geology, 7(2), 35-44
  • Sudiana, I. K. (2008). Patobiologi molekuler kanker. Penerbit Salemba.
  • Sudiana, I. K. (2014). Imunopatobiologi molekuler. Surabaya: Airlangga University Press. Hal, 23-33.
  • Sudiana, I.(2017). Hantaran Sinyal pada prosteosarkomaes Inflamasi. 1st ed. Surabaya: Airlangga University Press; pp. 32-35, 62-63.
  • Wang, R., Lu, M., Chen, H., Chen, S., Luo, X., Qin, Y., & Zhang, J. (2011). Increased IL-10 mRNA expression in tumor-associated macrophage correlated with late stage of lung cancer. Journal of Experimental & Clinical Cancer Research, 30(1), 62.
  • Xu, M., Xu, S. F., & Yu, X. C. (2014). Clinical analysis of osteosarcoma patients treated with high-dose methotrexate-free neoadjuvant chemotherapy. Current oncology, 21(5), e678.
  • Yang, L., & Zhang, Y. (2017). Tumor-associated macrophages, potential targets for cancer treatment. Biomarker research, 5(1), 25.


This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.