Figures & data
Figure 1. Involvement of autophagy in cancer therapy-relevant immunogenic cell death (ICD). In response to a selected panel of chemotherapeutics (including anthracyclins and oxaliplatin), cancer cells manifest two premortem stress responses [endoplasmic reticulum, (ER) stress and autophagy]. ER stress is required for the pre-apoptotic exposure of calreticulin (CRT) on the cell surface, whereas autophagy is necessary for the active secretion of ATP. Please note that autophagy alone cannot trigger ATP release, which also relies on the apoptosis-related activation of caspases. In this setting, secondary necrosis accounts for the release of HMGB1. CRT, ATP and HMGB1 act on specific receptors on the surface of antigen-presenting cells, mainly dendritic cells (DCs), to stimulate immune-relevant processes: engulfment, which depends on the interaction between CRT and a hitherto unidentified receptor; recruitment of immune effectors into the tumor bed and activation of the NLRP3 inflammasome, allowing for the release of mature interleukin-1β (IL-1β), both of which rely on the ATP-mediated activation of purinergic receptors; and tumor antigen presentation, which is stimulated by the HMGB1-mediated activation of Toll-like receptor 4 (TLR4). These processes ultimately result in the priming or re-activation of tumor antigen-specific T cells that can control the residual disease.
![Figure 1. Involvement of autophagy in cancer therapy-relevant immunogenic cell death (ICD). In response to a selected panel of chemotherapeutics (including anthracyclins and oxaliplatin), cancer cells manifest two premortem stress responses [endoplasmic reticulum, (ER) stress and autophagy]. ER stress is required for the pre-apoptotic exposure of calreticulin (CRT) on the cell surface, whereas autophagy is necessary for the active secretion of ATP. Please note that autophagy alone cannot trigger ATP release, which also relies on the apoptosis-related activation of caspases. In this setting, secondary necrosis accounts for the release of HMGB1. CRT, ATP and HMGB1 act on specific receptors on the surface of antigen-presenting cells, mainly dendritic cells (DCs), to stimulate immune-relevant processes: engulfment, which depends on the interaction between CRT and a hitherto unidentified receptor; recruitment of immune effectors into the tumor bed and activation of the NLRP3 inflammasome, allowing for the release of mature interleukin-1β (IL-1β), both of which rely on the ATP-mediated activation of purinergic receptors; and tumor antigen presentation, which is stimulated by the HMGB1-mediated activation of Toll-like receptor 4 (TLR4). These processes ultimately result in the priming or re-activation of tumor antigen-specific T cells that can control the residual disease.](/cms/asset/90e5797a-e669-4f55-831e-73349cf6b48b/kaup_a_10919009_f0001.gif)