Targeting HDL in tumor microenvironment: New hope for cancer therapy

J Cell Physiol. 2021 Nov;236(11):7853-7873. doi: 10.1002/jcp.30412. Epub 2021 May 21.

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.

Keywords: angiogenesis; high-density lipoprotein; immune cells; therapy; tumor microenvironment.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Angiogenesis Inhibitors / therapeutic use*
  • Animals
  • Anti-Inflammatory Agents / therapeutic use*
  • Cholesterol, HDL / metabolism
  • Humans
  • Hypolipidemic Agents / therapeutic use
  • Inflammation Mediators / antagonists & inhibitors*
  • Inflammation Mediators / metabolism
  • Lipoproteins, HDL / metabolism*
  • Lipoproteins, HDL / therapeutic use*
  • Neoplasms / drug therapy*
  • Neoplasms / immunology
  • Neoplasms / metabolism
  • Neoplasms / pathology
  • Neovascularization, Pathologic*
  • Recombinant Proteins / therapeutic use
  • Tumor Microenvironment* / immunology
  • Up-Regulation

Substances

  • Angiogenesis Inhibitors
  • Anti-Inflammatory Agents
  • Cholesterol, HDL
  • Hypolipidemic Agents
  • Inflammation Mediators
  • Lipoproteins, HDL
  • Recombinant Proteins