Lipidomic-based advances in diagnosis and modulation of immune response to cancer

Abstract

While immunotherapies for diverse types of cancer are effective in many cases, relapse is still a lingering problem. Like tumor cells, activated immune cells have an anabolic metabolic profile, relying on glycolysis and the increased uptake and synthesis of fatty acids. In contrast, immature antigen-presenting cells, as well as anergic and exhausted T-cells have a catabolic metabolic profile that uses oxidative phosphorylation to provide energy for cellular processes. One goal for enhancing current immunotherapies is to identify metabolic pathways supporting the immune response to tumor antigens. A robust cell expansion and an active modulation via immune checkpoints and cytokine release are required for effective immunity. Lipids, as one of the main components of the cell membrane, are the key regulators of cell signaling and proliferation. Therefore, lipid metabolism reprogramming may impact proliferation and generate dysfunctional immune cells promoting tumor growth. Based on lipid-driven signatures, the discrimination between responsiveness and tolerance to tumor cells will support the development of accurate biomarkers and the identification of potential therapeutic targets. These findings may improve existing immunotherapies and ultimately prevent immune escape in patients for whom existing treatments have failed.