Immune checkpoints in osteosarcoma: Recent advances and therapeutic potential

Osteosarcoma is the most common primary malignant bone tumor and is associated with a high risk of recurrence and distant metastasis. Effective treatment for osteosarcoma, especially advanced osteosarcoma, has stagnated over the past four decades. The advent of immune checkpoint inhibitor (ICI) has transformed the treatment paradigm for multiple malignant tumor types and indicated a potential therapeutic strategy for osteosarcoma. In this review, we discuss recent advances in immune checkpoints, including programmed cell death protein-1 (PD-1), programmed cell death protein ligand-1 (PD-L1), and cytotoxic T lymphocyte-associated antigen-4 (CTLA-4), and their related ICIs for osteosarcoma treatment. We present the main existing mechanisms of resistance to ICIs therapy in osteosarcoma. Moreover, we summarize the current strategies for improving the efficacy of ICIs in osteosarcoma and address the potential predictive biomarkers of ICIs treatment in osteosarcoma.