Abstract
Osteosarcoma (OS) is a high-grade malignant stromal tumor composed of mesenchymal cells producing osteoid and immature bone, with a peak of incidence in the second decade of life. Hence, although relatively rare, the social impact of this neoplasm is particularly relevant. Differently from carcinomas, molecular genetics and the role of the tumor microenvironment in the development and progression of OS are mainly unknown. Indeed, while the tumor microenvironment has been widely studied in other solid tumor types and its contribution to tumor progression has been definitely established, tumor–stroma interaction in OS has been quite neglected for years. Only recently have new insights been gained, also thanks to the availability of new technologies and bioinformatics tools. A better understanding of the cross-talk between the bone microenvironment, including immune and stromal cells, and OS will be key not only for a deeper knowledge of osteosarcoma pathophysiology, but also for the development of novel therapeutic strategies. In this review, we summarize the current knowledge about the tumor microenvironment in OS, mainly focusing on immune cells, discussing their role and implication for disease prognosis and treatment response.
Highlights
Osteosarcoma (OS), the most frequent bone tumor in children and adolescents, is a high-grade malignancy characterized by the formation of an osteoid matrix and immature bone, mainly in the metaphysis and diaphysis of long bones [1]
The precise cell of origin for OS is still unclear, some evidence indicates that it could arise from mesenchymal stem cells (MSCs) or from osteoblastic progenitors unable to proceed to terminal differentiation [4]
Higher CD14+ tumor-associated macrophages (TAMs) levels correlated with better OS and metastasis suppression with no clinical relevance between M1/M2 phenotype
Summary
Osteosarcoma (OS), the most frequent bone tumor in children and adolescents, is a high-grade malignancy characterized by the formation of an osteoid matrix and immature bone, mainly in the metaphysis and diaphysis of long bones [1]. Bone marrow opment and progression of OS is still lacking While it has been widely studied in (BM) is a very specialized microenvironment, containing highly heterogeneous cell types, other solid tumor types and its contribution to tumor progression has definitely been ranging from hematopoietic cellsinteraction to mesenchymal, neuronal cells. Review tries tomicroenvironment, summarize the state of thehighly art ofhetthe TME in bone marrow (BM)This is a very specialized containing erogeneous cell types, ranging from hematopoietic cells to mesenchymal, vascular, and OS, with a particular focus on tumor-infiltrating immune cells and their correlation with neuronal cells. This review tries to summarize the state of the art of theBone Microenvironment cells and their correlation with patients’ prognosis and response to treatment. From other primary tumors, the tumor microenvironment of OS is the BM, a highly environment composed of bone cells, immune cells, and stromal and
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