胶质瘤的免疫治疗研究进展

Recent advance in immunotherapy for glioblastoma multiforme

肿瘤免疫治疗是利用机体免疫系统特定地识别杀伤恶性细胞的能力而开发出来的一种新领域治疗方法。相对于既往常规化疗药物，其具有高度特异性和机体损害较少的特点，并且一旦机体形成对肿瘤的免疫攻击．这种杀伤恶性细胞的效应较常规化疗药物更为持久。由于颅内特殊的微环境，胶质瘤的免疫治疗也有一定特殊性。目前已发现大量的胶质瘤突变癌抗原以及促进机体针对肿瘤免疫反应的靶点分子主要集中在多肽疫苗、树突状细胞、CAR—T细胞、热休克蛋白、调节性T细胞的调控、PD-1／PD-L1、CTLA-4等信号通路上，并在分子生物学实验、动物实验甚至早期临床试验中都展现一定的抗肿瘤效果，但尚无明确的随机双盲等更高级别证据支持。未来胶质瘤免疫治疗的重点仍然在于肿瘤抗原疫苗的联合治疗以及T细胞调定点的调控上。

Cancer immunotherapy is an emerging method to recognize and kill malignant cells by the ability of intrinsic immune system. Immunotherapy for glioblastoma promises the possibility of highly specific and less toxic treatment as compared with conventional chemotherapy, and immunotherapy has more lasting efficacy once immunologic memory forms. The immunotherapy for glioblastoma has faced many barriers because of specific characteristics of microenvironment in the brain. There are numerous mutant targets expressed in glioma cells and therapeutic agents that boost antitumor immune response such as peptide vaccines, dendritic cell vaccines, heat shock protein vaccines, regulation of regulatory T cells, tumor-associated PD-L1 expression, and CTLA-4 signaling, which have been proved to facilitate efficacy of killing tumor cells in vivo and in vitro, even at early phase clinical trials; but no therapy has yet been proved to improve survival in a randomized, controlled trials. The key of immunotherapy for glioblastoma is still the combination therapy of tumor antigen vaccine and T cell checkpoint therapy in the future.