Figure 1.

Mechanism of immunogenic cell death (ICD). In response to ICD-inducing chemotherapeutics, tumor cells expose CRT on their surface at a pre-apoptotic stage, secrete ATP during apoptosis, and release HMGB1 during secondary necrosis. These damage-associated molecular pattern (DAMP) molecules liberated from dying tumor cells stimulate the recruitment of DCs into the tumor bed, the uptake and processing of tumor antigens, and the optimal antigen presentation to T cells. However, the binding of cell-surface CD47 to SIRP$\alpha$ on DCs inhibits their phagocytic function. Phagocytosis of tumor cells requires both the activation of pro-phagocytic signals as well as simultaneous disruption of the anti-phagocytic signal CD47. Cross-priming of CD8+ CTLs is triggered by mature DCs and γδ T cells in an IL-1β- and IL-17-dependent manner. Primed CTLs elicit direct cytotoxic response and kill remaining tumor cells through the generation of IFN-γ, perforin-1 and granzyme B.