前蛋白转化酶枯草杆菌蛋白酶/kexin 9 型 (PCSK9) 是一种众所周知的胆固醇代谢和心血管疾病调节因子，最近因其在癌症生物学中的新兴参与而受到关注。 PCSK9 的多功能性质不仅限于脂质调节，还涵盖可以影响癌症进展的广泛细胞过程。研究表明，PCSK9 可以调节 PI3K/Akt、MAPK 和 Wnt/β-catenin 等信号通路，从而影响细胞增殖、存活和血管生成。此外，PCSK9 和胆固醇稳态之间的相互作用可能会影响膜动力学和细胞迁移，进一步影响肿瘤的侵袭性。免疫系统在监测和控制癌症中的核心作用越来越受到人们的认可。最近的研究表明 PCSK9 能够通过与免疫细胞和肿瘤微环境成分的相互作用来调节免疫反应。这包括对树突状细胞成熟、T 细胞激活和细胞因子产生的影响，表明在形成抗肿瘤免疫反应中发挥作用。此外，PCSK9 对 PD1/PD-L1 等免疫检查点的潜在影响为其免疫调节功能增添了一层复杂性。人们对癌症免疫疗法的兴趣日益浓厚，促使人们探索靶向 PCSK9 以获得治疗益处的潜力。临床前研究已经证明 PCSK9 抑制剂和已建立的免疫疗法之间具有协同作用，为联合治疗提供了新的途径。对 PCSK9 进行策略性调控以增强肿瘤免疫并改善治疗效果为进一步研究提供了一个令人兴奋的领域。了解 PCSK9 影响癌症生物学和免疫的机制为开发新型免疫治疗方法带来了希望。本综述旨在对 PCSK9、癌症发病机制、肿瘤免疫以及免疫治疗干预的潜在影响之间的复杂联系进行全面分析。© 2024。作者获得 Springer Science Business Media, LLC 的独家许可，部分施普林格自然。

Proprotein convertase subtilisin/kexin type 9 (PCSK9), a well-known regulator of cholesterol metabolism and cardiovascular diseases, has recently garnered attention for its emerging involvement in cancer biology. The multifunctional nature of PCSK9 extends beyond lipid regulation and encompasses a wide range of cellular processes that can influence cancer progression. Studies have revealed that PCSK9 can modulate signaling pathways, such as PI3K/Akt, MAPK, and Wnt/β-catenin, thereby influencing cellular proliferation, survival, and angiogenesis. Additionally, the interplay between PCSK9 and cholesterol homeostasis may impact membrane dynamics and cellular migration, further influencing tumor aggressiveness. The central role of the immune system in monitoring and controlling cancer is increasingly recognized. Recent research has demonstrated the ability of PCSK9 to modulate immune responses through interactions with immune cells and components of the tumor microenvironment. This includes effects on dendritic cell maturation, T cell activation, and cytokine production, suggesting a role in shaping antitumor immune responses. Moreover, the potential influence of PCSK9 on immune checkpoints such as PD1/PD-L1 lends an additional layer of complexity to its immunomodulatory functions. The growing interest in cancer immunotherapy has prompted exploration into the potential of targeting PCSK9 for therapeutic benefits. Preclinical studies have demonstrated synergistic effects between PCSK9 inhibitors and established immunotherapies, offering a novel avenue for combination treatments. The strategic manipulation of PCSK9 to enhance tumor immunity and improve therapeutic outcomes presents an exciting area for further investigations. Understanding the mechanisms by which PCSK9 influences cancer biology and immunity holds promise for the development of novel immunotherapeutic approaches. This review aims to provide a comprehensive analysis of the intricate connections between PCSK9, cancer pathogenesis, tumor immunity, and the potential implications for immunotherapeutic interventions.© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.