Chaochu Cui,1,* Aiwei Yan,1,* Shengming Huang,1,2 Yifan Chen,1 Jinyu Zhao,1 Cixia Li,1,3 Xianwei Wang,1 Jianbo Yang1,4 

1Henan Key Laboratory of Medical Tissue Regeneration, Xinxiang Medical University, Xinxiang, Henan, People’s Republic of China; 2Rudong County Hospital of Traditional Chinese Medicine, Nantong, Jiangsu, People’s Republic of China; 3School of Life Sciences and Technology, Xinxiang Medical University, Xinxiang, Henan, People’s Republic of China; 4School of Medical Technology, Xinxiang Medical University, Xinxiang, Henan, 453003, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Xianwei Wang; Jianbo Yang, Email Wangxianwei1116@126.com; Yangjianbo12@126.com

Abstract: Cancer remains the foremost cause of mortality on a global scale. Immunotherapy has yielded remarkable outcomes in the fight against cancer and is regarded as one of the most crucial and promising therapeutic modalities. PCSK9, a critical target for plasma lipids control, has been extensively and deeply studied in multiple diseases. Currently, the functions of PCSK9 in cancer, particularly its immunomodulatory role, have been progressively revealed. PCSK9 is capable of modulating a variety of immune response throughout tumor progression by orchestrating lipid metabolism. Moreover, PCSK9 governs the cell fate of diverse immune cells, such as inflammatory factor signals, MHC signals, and TCR signals. This review comprehensively summarizes the current state of knowledge regarding the role and underlying mechanisms of PCSK9 in tumorigenesis, progression, immune escape, and drug resistance.

Keywords: PCSK9, lipid metabolism, immunotherapy, cancer