程序性细胞死亡蛋白1抑制剂抵抗在骨肉瘤治疗中的研究进展

The research progress of PD-1 inhibitor resistance in the treatment of osteosarcoma

骨肉瘤(osteosarcoma,OS)是儿童和青少年中最常见的原发性恶性骨肿瘤[1]。目前的主流治疗方案是:手术切除原发肿瘤联合新辅助化疗和辅助化疗。标准的治疗使局限性骨肉瘤患者的5年生存率提高到了70%,但是对复发性或转移性骨肉瘤的治疗效果不理想[2]。

In tumor tissues, there are various types of immune checkpoints, including programmed cell death protein 1( PD-1), programmed cell death protein ligand 1( PD-L1) and cytotoxic T lymphocyte associated protein 4( CTLA-4). These immune checkpoints can help tumor cells realize immune escape by inhibiting the function of immune cells, so as to promote the occurrence, development and metastasis of tumors. The emergence of immune checkpoint inhibitors, such like the clinical application of PD-1 inhibitors, has improved the prognosis of patients with certain types of tumors, such as melanoma, renal cell carcinoma, non-small cell lung cancer, and further improved the overall survival rate. However, the current research data showed that the therapeutic effect of PD-1 inhibitor on osteosarcoma was not satisfactory, and there was a phenomenon that being insensitive to inhibitors or drug resistance. Therefore, it is particularly important to fully understand the mechanism of PD-1 inhibitor in osteosarcoma, especially the resistance mechanism in osteosarcoma treatment. This paper reviews the mechanism of PD-1 inhibitor resistance in osteosarcoma and the methods to overcome the resistance in recent years, in order to provide new ideas for immunotherapy of osteosarcoma.