免疫疗法
癌症研究
PD-L1
癌症免疫疗法
肿瘤微环境
免疫系统
封锁
免疫检查点
细胞毒性T细胞
前蛋白转化酶
T细胞
药理学
化学
生物
低密度脂蛋白受体
受体
免疫学
胆固醇
脂蛋白
生物化学
体外
作者
Shengbo Sun,Jingxin Ma,Tingting Zuo,Jinyao Shi,Liting Sun,Cong Meng,Wenlong Shu,Zhengyang Yang,Hongwei Yao,Zhongtao Zhang
出处
期刊:Research
[American Association for the Advancement of Science]
日期:2024-01-01
卷期号:7: 0488-0488
被引量:17
标识
DOI:10.34133/research.0488
摘要
Immune checkpoint therapy, such as programmed cell death protein 1/programmed death-ligand 1 (PD-1/PD-L1) blockade, has achieved remarkable results in treating various tumors. However, most cancer patients show a low response rate to PD-1/PD-L1 blockade, especially those with microsatellite stable/mismatch repair-proficient colorectal cancer subtypes, which indicates an urgent need for new approaches to augment the efficacy of PD-1/PD-L1 blockade. Cholesterol metabolism, which involves generating multifunctional metabolites and essential membrane components, is also instrumental in tumor development. In recent years, inhibiting proprotein convertase subtilisin/kexin type 9 (PCSK9), a serine proteinase that regulates cholesterol metabolism, has been demonstrated to be a method enhancing the antitumor effect of PD-1/PD-L1 blockade to some extent. Mechanistically, PCSK9 inhibition can maintain the recycling of major histocompatibility protein class I, promote low-density lipoprotein receptor-mediated T-cell receptor recycling and signaling, and modulate the tumor microenvironment (TME) by affecting the infiltration and exclusion of immune cells. These mechanisms increase the quantity and enhance the antineoplastic effect of cytotoxic T lymphocyte, the main functional immune cells involved in anti-PD-1/PD-L1 immunotherapy, in the TME. Therefore, combining PCSK9 inhibition therapy with anti-PD-1/PD-L1 immunotherapy may provide a novel option for improving antitumor effects and may constitute a promising research direction. This review concentrates on the relationship between PCSK9 and cholesterol metabolism, systematically discusses how PCSK9 inhibition potentiates PD-1/PD-L1 blockade for cancer treatment, and highlights the research directions in this field.
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