TLR4 and neoplasm: Three distinct arms orchestrate ICD in dying tumor cells and are required for immune priming and activation: (1) the cell surface translocation of calreticulin (CRT, an ER residing protein chaperone and potent DC “eat me” signal), and the extracellular release of (2) HMGB1 (a DNA binding protein and TLR-4 mediated DC activator) and (3) ATP (an activator of the DC P2X7 purinergic receptor that triggers DC inflammasome activation, secretion of IL-1β, and subsequent priming of IFNγ producing CD8+ T cells) (Figure 4) (Ma et al., 2010).