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-α (TNF-α). At the same time, production of appropriate amounts of
IL-6 and TNF-α 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-α 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-α 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 γδ 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.