Can Bioactive Lipids Augment Anti-cancer Action of Immunotherapy and Prevent Cytokine Storm?

It is desired to selectively kill tumor cells with little or no action on normal cells. Current treatment options are associated with significant side effects including therapy with immune check point inhibitors (ICI). ICI therapy induced side effects are due to excess production of pro-inflammatory cytokines interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha). At the same time, production of appropriate amounts of IL-6 and TNF-alpha are needed to eliminate tumor cells. Hence, methods are needed that can selectively eliminate tumor cells and tone down the side effects of cytokine storm. Studies showed that IL-6 and TNF-alpha activate phospholipases to induce the release of polyunsaturated fatty acids (PUFAs) from the cell membrane phospholipid pool. PUFAs form precursors to pro-and anti-inflammatory eicosanoids and are capable of suppressing IL-6 and TNF-alpha excess production. PUFAs are endowed with capacity to selectively kill tumor cells by augmenting free radical generation and accumulation of toxic lipid peroxides in tumor but not normal cells. NK cells, TILs (tumor infiltrating cells) and gamma delta, T cells release toxic granules (also called as cytolytic granules) that contain unsaturated fatty acids localized between the granule delimiting membrane and the granule core. Thus, lipids are a universal component of cytolytic granules and play an important role in their cytotoxic actions. Based on this evidence, it is suggested that a combination of ICI/TILs and PUFAs may form a novel method of eliminating cancer with few side effects. (C) 2019 IMSS. Published by Elsevier Inc.