Mass-spectrometric characterization of peroxidized and hydrolyzed lipids in plasma and dendritic cells of tumor-bearing animals

Dendritic cells are the most potent antigen presenting cells responsible for the development of immune responses in cancer. However, it is known that the function of dendritic cells in tumor-bearing hosts is severely compromised. Our previous studies demonstrated that the defects in dendritic cell function are due, to a large extent, to the accumulation of high amounts of lipids – predominantly triglycerides – in a substantial proportion of dendritic cells in tumor-bearing mice and patients with cancer. The dendritic cells accumulation of lipids is likely associated with their up-regulation of a scavenger receptor A. This receptor is primarily responsible for uptake of modified lipids. Here, by using different versions of liquid chromatography–mass spectrometry, we identified several molecular species of oxygenated lipids in plasma of tumor-bearing animals that may be responsible for their uptake and accumulation by dendritic cells via scavenger receptor A-dependent pathway – the effect that may be associated with the loss of dendritic cell’s immune surveillance function in cancer.

► Elevation of oxygenated fatty acids in plasma of tumor-bearing mice. ► Accumulation of oxygenated fatty acids in dendritic cells of tumor-bearing mice. ► MS detection of oxygenated linoleic, arachidonic and docosahexaenoic acids. ► Decreased uptake of oxygenated fatty acids in Msr1−/− dendritic cells.