The Immune Landscape of Osteosarcoma: Implications for Prognosis and Treatment Response

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.

Baicalin induces apoptosis and autophagy in human osteosarcoma cells by increasing ROS to inhibit PI3K/Akt/mTOR, ERK1/2 and β-catenin signaling pathways

“…Osteosarcoma is the most common form of bone malignancy and derives from primitive bone-forming mesenchymal cells. At present, surgical resection is the primary means of treating patients with osteosarcoma [44] . Remarkably, the active ingredients of natural compounds also have an essential function in osteosarcoma treatment [45] .…”

Paediatric Strategy Forum for medicinal product development of multi-targeted kinase inhibitors in bone sarcomas

“…The use of mTKIs rather than a single-targeted TKI can therefore be preferable given that resistance is theoretically less likely to develop quickly with mTKIs as they inhibit multiple targets simultaneously [22]. mTKIs have a complex effect on tumour cell biology, angiogenesis, and the immune microenvironment [26], which pose further challenges in interpreting which specific receptor is relevant, and if simultaneous inhibition of receptors is needed [12e14]. The complexity of bone sarcoma microenvironments poses unique challenges for preclinical evaluation of these mTKIs.…”

“…An additional limitation in this regard is the lack of samples for biomarker analyses at initial diagnosis and relapse, given that prior treatment can also alter the tumour microenvironment. In summary, there is an increasing knowledge of the genetics of bone sarcomas, particularly how EWSR1:ETS fusions in Ewing sarcoma drive tumourigenicity [26,27]. However, robust evidence for the role of specific kinase dependencies in either osteosarcoma or Ewing sarcoma cells is lacking.…”

ATG16L1 is a Potential Prognostic Biomarker and Immune Signature for Osteosarcoma: A Study Based on Bulk RNA and Single-Cell RNA-Sequencing

“… 6–8 Use of chemotherapy activates autophagy in tumor cells, which accelerates development of resistance to drug cytotoxicity and renders cancer cells insensitive to treatment. 9 Use of autophagy inhibitors in combination with anti-tumor drugs can have greater anti-tumor effects by Increasing the sensitivity of osteosarcoma cells to drugs. 10 …”