Targeting HDL in tumor microenvironment: New hope for cancer therapy

Abstract

Epidemiological studies have shown that plasma HDL-C levels are closely related to the risk of prostate cancer, breast cancer, and other malignancies. As one of the key carriers of cholesterol regulation, high-density lipoprotein (HDL) plays an important role in tumorigenesis and cancer development through anti-inflammation, antioxidation, immune-modulation, and mediating cholesterol transportation in cancer cells and noncancer cells. In addition, the occurrence and progression of cancer are closely related to the alteration of the tumor microenvironment (TME). Cancer cells synthesize and secrete a variety of cytokines and other factors to promote the reprogramming of surrounding cells and shape the microenvironment suitable for cancer survival. By analyzing the effect of HDL on the infiltrating immune cells in the TME, as well as the relationship between HDL and tumor-associated angiogenesis, it is suggested that a moderate increase in the level of HDL in vivo with consequent improvement of the function of HDL in the TME and induction of intracellular cholesterol efflux may be a promising strategy for cancer therapy.

Dicarbonyl-modified lipoproteins contribute to proteinuric kidney injury

“…conditions include e.g. sepsis, diabetes, obesity, rheumatoid arthritis, and cancer (13,32). Kidney disease changes apoAI/HDL metabolism in ways that lead to lower levels and altered composition of apoAI/HDL that impairs the functionality of the particles (13).…”

“…ApoAI/HDL also regulates inflammation, oxidation, proliferation, apoptosis, and vasodilation, processes that pertain to conditions beyond classic cardiovascular diseases, such as stroke, cardiac events, and atherosclerosis. These additional conditions include, e.g., sepsis, diabetes, obesity, rheumatoid arthritis, and cancer ( 13 , 32 ). Kidney disease changes apoAI/HDL metabolism in ways that lead to lower levels and altered composition of apoAI/HDL that impairs the functionality of the particles ( 13 ).…”

Circulating Lipid- and Inflammation-Based Risk (CLIR) Score: A Promising New Model for Predicting Outcomes in Complete Colorectal Liver Metastases Resection

“… 31 , 90 , 91 (5) HDL-C and LDL-C have been indicated as potential immunomodulators. 60 , 92 Alterations in intracellular cholesterol homeostasis will affect immune cell function. 93 LDL-C has been reported to enhance the function of immune-suppressive cells, such as myeloid-derived suppressor cells (MDSCs) and T-regulatory cells (Tregs), and inhibit the cytotoxic T-lymphocytes (CTLs), natural killer (NK) cells, and antigen-presenting cells such as dendritic cells (DCs).…”

Effects of Serum Lipids on the Long-Term Prognosis of Ampullary Adenocarcinoma Patients after Curative Pancreatoduodenectomy

“…In addition, HDL-C also induces multiple alterations at the cellular level, such as cholesterol exhaustion in TAM, thereby weakening the tumor promoting effect of TAM [ 34 ]. Moreover, serum lipids are observed to enhance the anti-inflammatory effect of neutrophil, the activation of CD8+T cell, and the survival of CD4+T cell, and inhibit tumor progression by strengthening the anti-tumor immune response [ 35 ]. Secondly, in inflammatory TME, HDL-C can suppress tubulogenesis and endothelial cell migration by downregulating the expression of VEGF, VEGFR2, and TNF-α, thereby inhibiting pathological angiogenesis [ 36 ].…”