Immunogenic cell death in cancer: concept and therapeutic implications

Table 1 Key aspects of regulated cell death variants

Mode	Morphology	Prototypic inducers	Core mediators	Note(s)
ADCD	Autophagic	n.d.	Autophagy	May involve components of the autophagy machinery rather than bona fide lysosomal degradation
Entotic cell death	Entotic	Cell detachment	Actomyosin Lysosomes	Independent of phagocytic activity in engulfing cells
Extrinsic apoptosis	Apoptotic	Death receptor signaling	CASP8 CASP3	Negatively regulated by CFLAR and XIAP, sometimes involving MOMP
Ferroptosis	Necrotic	Erastin	ACSL4 LPCAT3	Iron-dependent, negatively regulated by GPX4 and FSP1
Intrinsic apoptosis	Apoptotic	DNA damage ER stress	BAK1 BAX CASP3	Demarcated by MOMP and negatively regulated by antiapoptotic BCL2 proteins
LDCD	Necrotic	Lysosomotropic agents	Cathepsins	Demarcated by primary LMP
MPT-driven necrosis	Necrotic	Ca2 + overload Oxidative stress	PPIF	Demarcated by MIMP and involving a poorly characterized multiprotein pore (PTPC)
Necroptosis	Necrotic	Death receptor signaling plus caspase inhibition Viral infection	RIPK1 RIPK3 MLKL	Negatively regulated by CASP8 and ADAR1
NETotic cell death	Necrotic	Pathogen infection	NADPH oxidases	Associated with NET extrusion
Parthanatos	Necrotic	PARP1 hyperactivation	AIFM1	Reflecting lethal NAD⁺ and ATP depletion

ADCD autophagy-dependent cell death, LDCD lysosome-dependent cell death, LMP lysosomal membrane permeabilization, MIMP mitochondrial inner membrane permeabilization, MOMP mitochondrial outer membrane permeabilization, MPT mitochondrial permeability transition, n.d. not determined, NET neutrophil extracellular trap, PTPC permeability transition pore complex
*Limited to main regulated cell death (RCD) modalities, adapted from Ref. [9]

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