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Current Understanding of PCSK9 and Its Relevance to Cancer Prognosis and Immune Therapy: A Review.

作者信息

Hassandokht Mashhadi Morteza, Taheri Fahime, Irani Sadaf, Mesbah Mousavi Arshiya, Mehri Ali, Javid Hossein

机构信息

Department of Medical Laboratory Sciences, Varastegan Institute for Medical Sciences, Mashhad, Iran.

Endoscopic and Minimally Invasive Surgery Research Center, Ghaem Hospital, Mashhad University of Medical Sciences, Mashhad, Iran.

出版信息

Iran J Pathol. 2024 Winter;19(1):1-9. doi: 10.30699/IJP.2023.1999459.3093. Epub 2023 Dec 29.


DOI:10.30699/IJP.2023.1999459.3093
PMID:38864086
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11164309/
Abstract

The effectiveness of immunotherapy for most cancer patients remains low, with approximately 10-30% of those treated surviving. Thus, much effort is being put into finding new ways to improve immune checkpoint therapy. Our review concludes that inhibition of proprotein convertase subtilisin/Kexin type 9 (PCSK9), which plays a critical role in regulating cholesterol metabolism, can cause movement of T cells 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: "PCSK9", "Cancer", "Immune Checkpoint", and "Cancer Prognosis" in the title and/or abstract. Our search initially revealed 600 records on the subject and stored them in the used databases under EndNote X8 management software. A total of 161 articles were selected and through a careful review, 76 were included in our research. We concluded that PCSK9 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 PCSK9 leads to the MHC-1 accumulation on the surface of cancer cells, which results in T lymphocyte invasion. Finally, we believe that inhibiting PCSK9 may be an effective strategy for improving cancer immunotherapy.

摘要
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d985/11164309/7552a41f1b18/ijp-19-1-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d985/11164309/9148818cccce/ijp-19-1-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d985/11164309/6a5807f37b76/ijp-19-1-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d985/11164309/7552a41f1b18/ijp-19-1-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d985/11164309/9148818cccce/ijp-19-1-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d985/11164309/6a5807f37b76/ijp-19-1-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d985/11164309/7552a41f1b18/ijp-19-1-g003.jpg

相似文献

[1]
Current Understanding of PCSK9 and Its Relevance to Cancer Prognosis and Immune Therapy: A Review.

Iran J Pathol. 2024

[2]
Targeting PCSK9 to upregulate MHC-II on the surface of tumor cells in tumor immunotherapy.

BMC Cancer. 2024-4-10

[3]
Targeting the proprotein convertase subtilisin/kexin type 9 for the treatment of dyslipidemia and atherosclerosis.

J Am Coll Cardiol. 2013-8-21

[4]
Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors: Present perspectives and future horizons.

Nutr Metab Cardiovasc Dis. 2016-10

[5]
Inhibition of PCSK9 potentiates immune checkpoint therapy for cancer.

Nature. 2020-12

[6]
Proprotein Convertase Subtilisin/Kexin Type 9 Inhibition: The Big Step Forward in Lipid Control.

Eur Cardiol. 2023-6-28

[7]
Proprotein Convertase Subtilisin/Kexin-Type 9 and Lipid Metabolism.

Adv Exp Med Biol. 2020

[8]
Antitumor activity and molecular mechanism of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibition.

Naunyn Schmiedebergs Arch Pharmacol. 2022-6

[9]
Cyclase-associated protein 1 is a binding partner of proprotein convertase subtilisin/kexin type-9 and is required for the degradation of low-density lipoprotein receptors by proprotein convertase subtilisin/kexin type-9.

Eur Heart J. 2020-1-7

[10]
Ascorbic acid enhances low-density lipoprotein receptor expression by suppressing proprotein convertase subtilisin/kexin 9 expression.

J Biol Chem. 2020-11-20

引用本文的文献

[1]
Inhibition of PCSK9: A Promising Enhancer for Anti-PD-1/PD-L1 Immunotherapy.

Research (Wash D C). 2024-9-25

[2]
Target therapy of TIGIT; a novel approach of immunotherapy for the treatment of colorectal cancer.

Naunyn Schmiedebergs Arch Pharmacol. 2025-1

本文引用的文献

[1]
Rewiring Lipid Metabolism by Targeting PCSK9 and HMGCR to Treat Liver Cancer.

Cancers (Basel). 2022-12-20

[2]
Association between genetically proxied PCSK9 inhibition and prostate cancer risk: A Mendelian randomisation study.

PLoS Med. 2023-1

[3]
PCSK9 in Liver Cancers at the Crossroads between Lipid Metabolism and Immunity.

Cells. 2022-12-19

[4]
Circulating levels of PCSK9, ANGPTL3 and Lp(a) in stage III breast cancers.

BMC Cancer. 2022-10-6

[5]
Bioinformatics Identification of Key Genes for the Development and Prognosis of Lung Adenocarcinoma.

Inquiry. 2022

[6]
Factors and Outcomes Associated With Venous Thromboembolism Following Bariatric Surgery.

Am Surg. 2022-10

[7]
Glioblastoma, an opportunity T cell trafficking could bring for the treatment.

Mol Biol Rep. 2022-10

[8]
Probiotics as an Adjuvant for Management of Gastrointestinal Cancers through their Anti-inflammatory Effects: A Mechanistic Review.

Curr Med Chem. 2023

[9]
Laparoscopic vs. Open Gastrectomy for Locally Advanced Gastric Cancer: A Propensity Score-Matched Retrospective Case-Control Study.

Curr Oncol. 2022-3-9

[10]
The Therapeutic Potential of Aprepitant in Glioblastoma Cancer Cells through Redox Modification.

Biomed Res Int. 2022

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