Wednesday, 01 December 2021 10:34

In vitro: Investigation of the cholesterol influence between tumor and its immune cells Featured

Using a self-developed in vitro model, scientists at Saarland University were able to show that the lipid and cholesterol metabolism of tumor-associated immune cells is severely impaired in contrast to that of tumor tissue.

It is known that higher cholesterol and lipid levels can be measured in tumor cells than in healthy cells, which is attributed to tumor-specific processes such as increased cell division. It is also known that tumor cells reprogram fighting immune cells to their own advantage. For the first time, the research team has demonstrated that tumor-associated macrophages contain significantly less cholesterol than macrophages of healthy tissue.

For their studies, pharmaceutical scientists professor Alexandra K. Kiemer and Dr. Jessica Hoppstädter from Saarland University developed an in vitro tumor model consisting of small-cell lung tumor tissue and, for comparison, healthy tissue from patients, each with integrated immune cells (macrophages). The researchers observed that in simulated tumor-associated macrophages, genes involved in cholesterol biosynthesis and cholesterol metabolism were downregulated, while cholesterol efflux transporters were upregulated.

The scientists interpreted this as opposing dysregulation of the physiological balance of cholesterol in tumor cells and tumor-associated immune cells. Furthermore, they observed that normalization of cholesterol levels in tumor-associated macrophages by preventing cholesterol efflux caused the macrophages to cease their tumor-favoring activities. This could be a building block for the development of a subsequent treatment strategy.

The research team published their findings in the journal EBioMedicine:
Jessica Hoppstädter, Anna Dembek, Marcus Höring, Hanna S Schymik, Charlotte Dahlem, Afnan Sultan, Natalie Wirth, Salma Al-Fityan, Britta Diesel, Gilles Gasparoni, Jörn Walter, Volkhard Helms, Hanno Huwer, Martin Simon, Gerhard Liebisch, Marcel H Schulz, Alexandra K Kiemer (2021). Dysregulation of cholesterol homeostasis in human lung cancer tissue and tumor-associated macrophages. EBioMedicine 72, 103578. doi: 10.1016/j.ebiom.2021.103578.