摘要INTRODUCTIONOsteosarcoma (OS), a common primary malignant bone tumor, mainly occurs in children and teenagers.1 Advances in surgical technology and neoadjuvant chemotherapy have significantly increased the overall survival rate of OS. Nevertheless, improving the survival rate of recurrent and metastatic diseases still remains a challenge (less than 30％ within two years).2 Immune checkpoint blockade (ICB) is regarded as a promising therapy for numerous solid tumors, including melanoma, non-small cell lung cancer and kidney cancer.3 Recently, immune checkpoint inhibitors that target PD-1 or CTLA-4 have also been tested in OS.4–6 However, only a limited number of patients have demonstrated a response to anti-PD-1 immunotherapy in recent clinical trials. Moreover, the impact of anti-CTLA-4 immunotherapy in clinical application for OS remains unclear.7 In OS, cancer cells interact with both immune cells and stromal cells to form an immunosuppressive tumor microenvironment (TME), thus enhancing cancer cell immune evasion. The inter-tumoral heterogeneity is also an important feature of OS, leading to treatment resistance and divergent therapeutic outcomes among patients.8 Understanding cancer cell heterogeneity as well as the dynamic tumor immune microenvironment could provide new therapeutic targets to treat OS.