Cholesterol and Immune Microenvironment: Path Towards Tumorigenesis.

Abstract

PURPOSE OF REVIEW:

Since obesity is a major risk factor for many different types of cancer, examining one of the most closely associated comorbidities, such as hypercholesterolemia, is crucial to understanding how obesity causes cancer. Hypercholesterolemia is usually associated with many cardiovascular complications such as hypertension, angina, and atherosclerosis. In addition, cholesterol may be a major factor in increasing cancer risk. Cancer patients who received statins, an anti-hypercholesteremic medicine, demonstrated improved prognosis possibly through its effect on tumor proliferation, apoptosis, and oxidative stress. Cholesterol could also aid in tumor progression through reprogramming tumor immunological architecture and mediators. This review focuses on the immunomodulatory role of cholesterol on cellular and molecular levels, which may explain its oncogenic driving activity. We look at how cholesterol modulates tumor immune cells like dendritic cells, T cells, Tregs, and neutrophils. Further, this study sheds light on the modification of the expression pattern of the common cancer-related immune mediators in the tumor immune microenvironment, such as programmed cell death 1 (PD-1), cytotoxic T lymphocyte antigen-4 (CTLA-4), transforming growth factor-beta (TGF-β), interleukin 12 (IL-12), IL-23, and forkhead box protein P3 (FOXP3).

RECENT FINDINGS:

We highlight relevant literature demonstrating cholesterol's immunosuppressive role, leading to a worse cancer prognosis. This review invites further research regarding the pathobiological role of cholesterol in many obesity-related cancers such as uterine fibroids, post-menopausal breast, colorectal, endometrial, kidney, esophageal, pancreatic, liver, and gallbladder cancers. This review suggests that targeting cholesterol synthesis may be a fruitful approach to cancer targeting, in addition to traditional chemotherapeutics.

• Authors: Eslam E Saad, Rachel Michel, Mostafa A Borahay
• Journal: Current nutrition reports (Curr Nutr Rep) (May 02 2024) ISSN: 2161-3311 [Electronic] United States
• PMID: 38696074 (Publication Type: Journal Article, Review)
• Copyright: © 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.