Role of lipids in tumor metabolic reprogramming

Cancer associated cachexia (CAC) accompanies up to 80% of cancer diseases, interferes with cancer therapy, and largely decreases survival of cancer patients. CAC is characterized by a metabolic imbalance favoring catabolism over anabolism which results in adipose tissue loss and muscle tissue atrophy. Importantly, CAC cannot be halted by increased nutritional intake. Currently no approved treatment for CAC is available also because the underlying mechanisms of the disease are not well understood. In CAC the tumor is at the center of the disease, however little is known about the differences between cachexigenic and non -cachexigenic tumors. Besides cancer cells, tumors consist of a variety of different cell types, including cells of the immune system, that together build up a unique tumor micro-environment (TME). We hypothesize that cancer cell metabolism changes the lipid composition of the TME which subsequently affects immune cell activation, promotes tumor growth, and inflammatory cytokine production, together leading to poor prognosis. We aim to delineate whether cancer cell metabolism determines the composition of the TME with regard to lipid metabolites and immune cell populations. By dissecting and analyzing different areas of a tumor at almost single cell resolution we are confident to identify novel signals and signaling pathways underlying immune infiltration, activation, and production of inflammatory cytokines. The combination of metabolic studies with high resolution lipidomics and mass spectrometric imaging represent a unique liaison for cancer research.