Lipoprotein Metabolism in Hematological Malignancies: A Role in Shaping the Tumor Cell Microenvironment?

TL;DR

This paper reviews how lipoprotein metabolism influences the tumor microenvironment in blood cancers, potentially promoting tumor growth and immune suppression.

Contribution

The paper provides a comprehensive review of lipoprotein metabolism's role in hematological malignancies and its impact on the tumor microenvironment.

Findings

Lipoprotein metabolism contributes to an immune-suppressive tumor microenvironment in blood cancers.

Abnormal lipoprotein levels are observed in leukemic patients, suggesting their importance for cancer cell survival.

Cholesterol and fatty acids from lipoproteins support tumor progression by reprogramming metabolism.

Abstract

The tumor microenvironment (TME) plays a key role in driving tumor progression, metastasis, and resistance to therapy. The TME is a highly variable ecosystem composed of both cancer and surrounding normal cells, immune survey cells and the extracellular matrix, also composed of signaling molecules that mediate interactions between them. Blood cancer cells pose a unique challenge because of their circulation and widespread distribution along with their capacity to invade various niches, interacting with a wide range of host cells such as fibroblasts, immune cells, endothelial cells, and adipocytes. Metabolism reprogramming in this tumor context, notably referring to elevated cholesterol and fatty acid metabolism, emerges as a crucial event in shaping an immune-suppressive microenvironment that promotes tumor progression. Cholesterol and fatty acids are supplied by both de novo biosynthesis and exogenous uptake from lipoproteins. Lipoproteins are pseudo-micellar structures, designed to transport essential water-insoluble metabolites, including triacylglycerols and cholesterol, in the plasma, lymph, and interstitial fluids. A number of studies have reported abnormal circulating lipoprotein levels in leukemic patients and have suggested that lipoproteins are key for cancer cells to thrive. However, the role of lipoprotein metabolism in cancer cells in the context of the TME is still incompletely discussed so far. The aim of this review is to consider the importance of lipoprotein metabolism in shaping the tumor microenvironment in the context of hematological malignancies.

Figures