The Role of Macrophages in Sarcoma Tumor Microenvironment and Treatment

SIMPLE SUMMARY: Soft tissue and bone sarcomas belong to a group of rare and malignant tumors. The treatment of these tumors is very complex and depends on their specific subtypes. Therefore, there is a great need to develop novel therapeutic options for patients with sarcomas. One such option may be to target tumor-associated macrophages (TAMs), which are involved in immunosuppression during tumor growth. High levels of TAMs are widely recognized as a poor prognostic factor in many tumors, including sarcomas, making them a promising target for future targeted therapies. In this review, we highlight the role of TAMs in the microenvironment of sarcomas, along with their clinical relevance, potential targetable markers on their surface, and the molecular pathways involved. We also discuss currently ongoing clinical trials with TAMs. ABSTRACT: Sarcomas are a heterogeneous group of malignant mesenchymal tumors, including soft tissue and bone sarcomas. Macrophages in the tumor microenvironment, involved in immunosuppression and leading to tumor development, are called tumor-associated macrophages (TAMs). TAMs are very important in modulating the microenvironment of sarcomas by expressing specific markers and secreting factors that influence immune and tumor cells. They are involved in many signaling pathways, such as p-STAT3/p-Erk1/2, PI3K/Akt, JAK/MAPK, and JAK/STAT3. TAMs also significantly impact the clinical outcomes of patients suffering from sarcomas and are mainly related to poor overall survival rates among bone and soft tissue sarcomas, for example, chondrosarcoma, osteosarcoma, liposarcoma, synovial sarcoma, and undifferentiated pleomorphic sarcoma. This review summarizes the current knowledge on TAMs in sarcomas, focusing on specific markers on sarcoma cells, cell–cell interactions, and the possibly involved molecular pathways. Furthermore, we discuss the clinical significance of macrophages in sarcomas as a potential target for new therapies, presenting clinical relevance, possible new treatment options, and ongoing clinical trials using TAMs in sarcoma treatment.