尽管采用了多模态治疗方法，在过去的几十年里，转移性或复发性骨肉瘤的治愈率并没有显著提高，在少于30%的病例中可以实现长期存活。骨肉瘤患者经常对化疗药物产生抗药性，个体化靶向治疗应该能够带来新的希望。T细胞免疫疗法作为一种互补或替代治疗方式，在总体上正在迅速发展，但其对骨肉瘤的潜力尚未得到充分探索。正在研究应用免疫检查点抑制剂（ICI）、嵌合抗原受体（CAR）改良T细胞和T细胞结合的双特异性抗体（BsAbs）等策略来应对复发或难治性骨肉瘤。然而，骨肉瘤在肿瘤内部和肿瘤间水平上都具有固有的异质性，不存在完全相同的驱动基因突变。它具有促肿瘤微环境，骨细胞、基质细胞、新生血管、抑制性免疫细胞和矿化的细胞外基质（ECM）共同作用，使T细胞的浸润能力和抗肿瘤功能受到破坏。为了充分发挥T细胞免疫疗法在骨肉瘤中的潜力，需要智能规划和执行一种综合方法来针对这个复杂的生态系统。在这里，我们对骨肉瘤的T细胞免疫疗法的当前状况进行了回顾，总结了遇到的挑战，并探讨了克服这些障碍的组合策略，以实现治愈骨肉瘤并减少急性和长期副作用的最终目标。

The cure rate for metastatic or relapsed osteosarcoma has not substantially improved over the past decades despite the exploitation of multimodal treatment approaches, allowing long-term survival in less than 30% of cases. Patients with osteosarcoma often develop resistance to chemotherapeutic agents, where personalized targeted therapies should offer new hope. T cell immunotherapy as a complementary or alternative treatment modality is advancing rapidly in general, but its potential against osteosarcoma remains largely unexplored. Strategies incorporating immune checkpoint inhibitors (ICIs), chimeric antigen receptor (CAR) modified T cells, and T cell engaging bispecific antibodies (BsAbs) are being explored to tackle relapsed or refractory osteosarcoma. However, osteosarcoma is an inherently heterogeneous tumor, both at the intra- and inter-tumor level, with no identical driver mutations. It has a pro-tumoral microenvironment, where bone cells, stromal cells, neovasculature, suppressive immune cells, and a mineralized extracellular matrix (ECM) combine to derail T cell infiltration and its anti-tumor function. To realize the potential of T cell immunotherapy in osteosarcoma, an integrated approach targeting this complex ecosystem needs smart planning and execution. Herein, we review the current status of T cell immunotherapies for osteosarcoma, summarize the challenges encountered, and explore combination strategies to overcome these hurdles, with the ultimate goal of curing osteosarcoma with less acute and long-term side effects.