Digging Through the Complexities of Immunological Approaches in Emerging Osteosarcoma Therapeutics: A Comprehensive Narrative Review with Updated Clinical Trials

Osteosarcoma (OS) is the predominant mesenchymal primary malignant bone tumor in oncology and pathology, impacting a wide age range from adolescents to older adults. It frequently advances to lung metastasis, ultimately resulting in the mortality of OS patients. The precise pathological pathways responsible for OS progression and dissemination are not fully understood due to its heterogeneity. The integration of surgery with neoadjuvant and postoperative chemotherapy has significantly increased the 5-year survival rate to more than 70% for patients with localized OS tumors. However, about 30% of patients experience local recurrence and/or metastasis. Hence, there is a requirement for innovative therapeutic approaches to address the limitations of traditional treatments. Immunotherapy has garnered increasing attention as a promising avenue for tumors resistant to standard therapies, including OS, despite the underlying mechanisms of disease progression and dissemination remaining not well elucidated. Immunotherapy may not have been suitable for use in patients with OS because of the tumor's immunosuppressive microenvironment and limited immunogenicity. Nevertheless, there are immune-based treatments now being developed for clinical use, such as bispecific antibodies, chimeric antigen receptor T cells, and immune checkpoint inhibitors. Also, additional immunotherapy techniques including cytokines, vaccines, and modified-Natural Killer (NK) cells/macrophages are in the early phases of research but will certainly be popular subjects in the nearest future. Our goal in writing this review was to spark new lines of inquiry into OS immunotherapy by summarizing the findings from both preclinical and current clinical studies examining different approaches.