Targeting HDL in tumor microenvironment: New hope for cancer therapy

• Published in: Journal of cellular physiology 2021-11, Vol.236 (11), p.7853-7873
• Main Authors: Zhao, Tan‐Jun, Zhu, Neng, Shi, Ya‐Ning, Wang, Yu‐Xiang, Zhang, Chan‐Juan, Deng, Chang‐Feng, Liao, Duan‐Fang, Qin, Li
• Format: Article
• Language: English
• Subjects: Angiogenesis; Breast cancer; Cancer therapies; Cholesterol; Cytokines; Efflux; Epidemiology; High density lipoprotein; immune cells; Immune system; Prostate cancer; therapy; Tumor microenvironment; Tumorigenesis; Tumors
• ISSN: 0021-9541; 1097-4652
• DOI: 10.1002/jcp.30412

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. The tumor microenvironment (TME) compose of tumor cells, nontumor cells, and extracellular matrix (ECM). HDL may play roles in cancer development by acting with both tumor and nontumor cells. In the submitted paper, we summarized clinical observations and carefully dissected possible mechanisms based on experimental data obtained in levels from cellular, organ, and genetically engineered animal models. 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.