Figure 1.

Strategies to convert non-immunogenic RCD into bona fide ICD. Upon inoculation into immunocompetent syngeneic hosts, cancer cells responding to a panel of lethal stimuli trigger an adaptive immune response against dead cell-associated antigens. Such an immunogenic variant of regulated cell death (RCD), commonly known as immunogenic cell death (ICD), relies on the exposure of calreticulin (CALR) on the cell surface, on the secretion of ATP, on the production of type I interferons (IFNs) and on the release of high-mobility group box 1 (HMGB1, which accompanies cell death). When any of these damage-associated molecular patterns cannot be emitted (in the appropriate spatiotemporal order), dying cancer cells cannot be perceived anymore as immunogenic by the host immune system. Several strategies have been conceived to correct these defects, hence converting non-immunogenic RCD into bona fide ICD. ER, endoplasmic reticulum; IFNAR, interferon (alpha, beta, and omega) receptor; P2RX7, purinergic receptor P2X, ligand gated ion channel, 7; P2RY2, purinergic receptor P2Y, G-protein coupled, 2; TLR, toll-like receptor.