Surface Markers and Chemokines/Cytokines of Tumor-Associated Macrophages in Osteosarcoma and Other Carcinoma Microenviornments—Contradictions and Comparisons.

Simple Summary: Osteosarcoma (OS) is the most frequently occurring malignant bone tumor in children. Although advances in chemotherapy and surgery have gradually improved OS prognosis, no improvement has been reported over the past two decades. Recently, tumor microenvironment (TME) has attracted attention as a novel therapeutic target. The TME includes peritumoral immune cells, blood vessels, extracellular matrix, fibroblasts, lymphocytes, bone marrow-derived inflammatory cells, platelets, and signaling molecules, which create an environment that promotes tumor growth, metastasis, and anticancer drug resistance. Research on the TME is particularly important because tumor-associated macrophages (TAMs) are a major component of this microenvironment, and the interaction between tumors and TAMs contributes towards tumor aggressiveness. However, our knowledge of the interaction between OS and TAMs is limited. In this review, we aim to describe the characteristics of TAMs in the OS TME. Osteosarcoma (OS) is the most common primary bone tumor in children and adolescents. Prognosis is improving with advances in multidisciplinary treatment strategies, but the development of new anticancer agents has not, and improvement in prognosis for patients with pulmonary metastases has stalled. In recent years, the tumor microenvironment (TME) has gained attention as a therapeutic target for cancer. The immune component of OS TME consists mainly of tumor-associated macrophages (TAMs). They exhibit remarkable plasticity, and their phenotype is influenced by the TME. In general, surface markers such as CD68 and CD80 show anti-tumor effects, while CD163 and CD204 show tumor-promoting effects. Surface markers have potential value as diagnostic and prognostic biomarkers. The cytokines and chemokines produced by TAMs promote tumor growth and metastasis. However, the role of TAMs in OS remains unclear to date. In this review, we describe the role of TAMs in OS by focusing on TAM surface markers and the TAM-produced cytokines and chemokines in the TME, and by comparing their behaviors in other carcinomas. We found contrary results from different studies. These findings highlight the urgency for further research in this field to improve the stalled OS prognosis percentages. [ABSTRACT FROM AUTHOR]