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Mammalian cells responding to specific perturbations of homeostasis can undergo a regulated variant of cell death that elicits adaptive immune responses. As immunogenic cell death (ICD) can only occur in a precise cellular and organismal context, it should be conceptually differentiated from instances of immunostimulation or inflammatory responses that do not mechanistically depend on cellular demise. Here, we critically discuss key conceptual and mechanistic aspects of ICD and its implications for cancer (immuno)therapy. [ABSTRACT FROM AUTHOR]

When cellular damage can be efficiently repaired and/or microenvironmental perturbations are limited in intensity and duration, cells can recover physiological functions in the context of re-established homeostasis [[2]]. These mechanisms encompass, but are not limited to: the DNA damage response [[4]], the unfolded protein response [[5]], and autophagy [[6]]. On the contrary, when damage is beyond repair and/or stressful stimuli are excessively intense or prolonged, the same pathways that initially attempt to restore physiological homeostasis instead engage signaling modules that actively promote cellular demise, a process that has been dubbed regulated cell death (RCD) [[1]]. Eukaryotic cells exposed to extreme perturbations of homeostasis, which are relatively rare in nature, succumb to the unregulated and virtually immediate physical breakdown of their components, a process that has been dubbed accidental cell death (ACD) [[1]]. [Extracted from the article]

BCL2 robustly preserves mitochondrial integrity, hence inhibiting innate immune signaling and apoptotic cell death in several cell types. Here, we comment on our recent data demonstrating that BCL2 also limits the ability of dendritic cells to elicit adaptive immune responses, lending support to a universal immunosuppressive function for the mitochondrial immune checkpoint. [ABSTRACT FROM AUTHOR]