Immunotherapy in pediatric bone sarcomas: Current progress and future directions

Pediatric bone sarcomas continue to present substantial therapeutic challenges in the metastatic, relapsed, or refractory setting, where clinical outcomes have remained largely static for decades despite advances in multimodal therapy. This review summarizes emerging immunotherapeutic strategies aimed at overcoming the immunosuppressive tumor microenvironment, low mutational burden and limited targetable antigens characteristic of these tumors. Current clinical investigations span multiple immunotherapeutic modalities, including adoptive natural killer cell therapies, cytokine-based immune priming, CAR T cell approaches and a growing array of RNA-based therapeutics. Checkpoint inhibitors are also under evaluation, particularly in combination with immunomodulatory or targeted agents. Collectively, these trials highlight both the promise and limitations of immunotherapy in pediatric sarcomas and underscore the need for deeper understanding of sarcoma immune biology to guide future, more effective therapeutic strategies.