PCSK9在肿瘤发生中的作用及其在免疫治疗中的潜在价值

前蛋白转化酶枯草杆菌素Kexin9型（proprotein convertase subtilisin/kexin type 9，PCSK9）是前蛋白转化酶（proprotein convertases，PCs）家族第九个成员，主要功能是结合细胞膜上低密度脂蛋白受体（low-density lipoprotein receptor，LDLR），介导LDLR降解，进而调节血浆低密度脂蛋白（low-density lipoprotein，LDL）水平。PCSK9通过调节肿瘤细胞增殖与凋亡、侵袭与迁移等多条途径促进肿瘤的发生发展，并与肿瘤微环境中CD8+T淋巴细胞等免疫细胞的浸润与功能、M2型巨噬细胞的迁移与极化密切相关，可作为联合化疗或免疫治疗等抗肿瘤治疗的靶点，其作用机制与调节肿瘤细胞凋亡因子、内质网应激、线粒体凋亡、调节免疫细胞脂质代谢等相关。本文就PCSK9在肿瘤发生中的作用及其机制以及PCSK9在肿瘤免疫治疗的潜在价值进行综述。 

Role of PCSK9 in tumor development and its potential value in immunotherapy

Proprotein convertase subtilisin/kexin type 9 (PCSK9) is the ninth member of the proprotein convertase (PC) family. Its main function is binding to low-density lipoprotein receptors (LDLRs) on the cell membrane. The binding mediates the degradation of LDLRs and subsequent regulation of plasma LDL levels. Increasing evidence from recent studies indicates that PCSK9 plays an important role in the occurrence and development of tumors by regulating tumor cell proliferation, apoptosis, invasion, and migration. PCSK9 is also closely related to the infiltration and function of immune cells, such as CD8+T lymphocytes in the tumor microenvironment, and the migration and polarization of M2 macrophages. PCSK9 can be used as a target for anti-tumor therapy and combined chemotherapy or immunotherapy. Its mechanism is associated with the regulation of apoptosis factors, endoplasmic reticulum stress, mitochondrial apoptosis of tumor cells, and lipid metabolism of immune cells. This article reviews the roles and mechanisms of PCSK9 in cancer and its potential value in cancer immunotherapy.