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Abstract

Osteosarcoma, the most prevalent primary malignant bone tumor in children and adolescents, remains a formidable clinical challenge due to its heterogeneous biology and resistance to conventional therapies. Despite advances in surgical and chemotherapeutic approaches, outcomes have plateaued over the past few decades, especially in metastatic and relapsed cases. Recent insights into tumor immunology have led to the exploration of immune checkpoint inhibitors and biomarker-driven strategies to personalize treatment. This article examines the role of immune checkpoints such as PD-1, PD-L1, and CTLA-4 in osteosarcoma, and how emerging biomarkers including tumor mutational burden, immune cell infiltration profiles, and circulating tumor DNA may enable more tailored and effective therapies. We discuss current research, clinical trials, and future prospects for integrating immunotherapy and biomarker science into routine osteosarcoma management.