细胞焦亡与药物治疗及免疫治疗在胶质母细胞瘤中的研究进展

Research Progress in Pyroptosis, Drug Therapy and Immunotherapy in Glioblastoma

关键词:  细胞焦亡  胶质母细胞瘤  免疫治疗  肿瘤微环境

Key words:  pyroptosis  glioblastoma  immunotherapy  tumor microenvironment

摘要:

细胞焦亡是一种由焦孔素家族介导的炎性细胞死亡方式，能够促进炎性介质的释放从而活化肿瘤微环境(tumor microenvironment，TME)中的NK细胞、T细胞、巨噬细胞等免疫细胞群发挥调控免疫抗肿瘤作用。胶质母细胞瘤(glioblastoma，GBM)是最严重、最恶性的胶质瘤，被诊断GBM的患者中位生存期<2年，并且由于血脑屏障的存在导致药物难以抵送至脑部从而影响药物抗GBM的作用。因此探索新的措施及机制来治疗GBM是十分重要的。GBM具有复杂的TME，其TME中存在大量的免疫细胞群，然而这些免疫细胞群往往受到GBM的影响处于免疫抑制状态。细胞焦亡作为一种能够激活免疫的细胞死亡方式，具有活化机体的免疫帮助逆转TME免疫抑制的作用。本综述以细胞焦亡为出发点阐述细胞焦亡与免疫系统之间的关系、细胞焦亡如何影响GBM的TME的免疫细胞群以及细胞焦亡途径在GBM治疗中的药物研究新进展，为未来临床治疗GBM提供新的方向和策略。

Abstract:

Pyroptosis, a form of inflammatory cell death mediated by the Gasdermins family, promotes the release of inflammatory mediators and activates immune cell populations such as NK cells, T cells and macrophages in the tumor microenvironment(TME) to exert immune-regulating and anti-tumor effects. Glioblastoma(GBM) is the most serious and malignant glioma, and the median survival of patients diagnosed with GBM is less than 2 years, and the presence of the blood-brain barrier makes it difficult to deliver drugs to the brain, thus affecting the effect of drugs against GBM. Therefore, it is important to explore new measures and mechanisms to treat GBM, which has a complex TME with a large number of immune cell populations that are often immunosuppressed by GBM. Cellular pyroptosis as a mode of cell death capable of activating immunity, has the effect of activating the body’s immunity to help reverse TME immunosuppression. This review will focus on the relationship between cell pyroptosis and the immune system, how cell pyroptosis affects the immune cell population of TME in GBM, and the new progress in drug research on cell pyroptosis pathways in GBM treatment, providing new directions and strategies for future clinical treatment of GBM.