Autophagy Links Pattern Recognition Receptors to Tumor Cell Apoptosis

Abstract

Pathogen nucleic acids are detected by the infected body’s immune cells via specific innate immune receptors, resulting in reactions such as secretion of T helper type 1 (Th1)-like and proinflammatory cytokines. Two studies have now reported the induction of cell death in melanoma cells, but not healthy skin cells, via stimulation of the cytoplasmic receptor MDA5 by the synthetic double-stranded RNA (dsRNA) agonist poly I:C, and one of the studies elucidated the mechanism for this response. Polyethyleneimine (PEI)-formulated poly I:C engages an intracellular process called autophagy via MDA5 to result in the induction of prodeath programs that ultimately lead to apoptosis of melanoma cells. Together with previous work, these reports demonstrate that immune detection of foreign nucleic acids involves diverse signaling pathways and thus yields different cellular outcomes that may overcome the inherent resistance of cancer cells to current cancer treatments.