Current Understanding of PCSK۹ and Its Relevance to Cancer Prognosis and Immune Therapy: A Review

The effectiveness of immunotherapy for most cancer patients remains low, with approximately ۱۰–۳۰% of those treated surviving. Thus, much effort is being put into finding new ways to improve immune checkpoint therapy. Our review concludes that the inhibition of proprotein convertase subtilisin/Kexin type ۹ (PCSK۹), which plays a critical role in regulating cholesterol metabolism, can cause T cells to move toward tumors, with increased sensitivity to immune checkpoint therapies.We searched PubMed, NCBI, Scopus, and Google Scholar for the published articles without limitations on publication dates. We used the following terms: “PCSK۹”, “Cancer”, “Immune Checkpoint”, and “Cancer Prognosis” in the title and/or abstract. Our search initially revealed ۶۰۰ records on the subject and stored them in the used databases under EndNote X۸ management software. We selected about ۱۶۱ articles that were carefully read and among them, ۷۶ were included in our research.We concluded that PCSK۹ reduces the number of LDL receptors (LDL-R) on the cell surface, which is linked to its ability to regulate cholesterol levels in the body. Also, we discuss how suppressing PCSK۹ leads to the MHC-۱ accumulation on the surface of cancer cells, which results in T lymphocyte invasion. Finally, we believe that inhibiting PCSK۹ may be an effective strategy for improving cancer immunotherapy.

Keywords:

PCSK۹ , Immunotherapy , Cancer , Immune checkpoint