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Table 1 Comparison of select cell death forms

From: Pyroptosis at the forefront of anticancer immunity

  Inducers Key constituents Characteristics Cell release Immune features
Apoptosis (PCD) TNF-α, FasL, TRAIL, Hypoxia, Irradiation, Heat shock Bcl-2 protein family, P53, Caspase-2/3/6/7/8/9/10, HSPs Plasma membrane blebbing, Reduced cellular volume, Nuclear fragmentation and chromatin condensation In certain cases:
DAMPs (e.g., dsDNA, HMGB1, ATP, calreticulin)
Mostly anti-inflammatory. Pro-inflammatory in cases involving the release of DAMPs
Pyroptosis (PCD) DAMPs, PAMPs, Microbial infection GSDM protein family, Caspase-1/3/4/5/8/11, Inflammasomes Plasma membrane rupture and pore formation, Cytoplasmic swelling, Chromatin condensation Intracellular content, DAMPs (e.g., IL-18, IL-1β, dsDNA, ATP, HMGB1) Pro-inflammatory
Necroptosis (PCD) TNF-α, TRAIL, Fas ligand, Microbial infection MLKL, RIPK1/3 (Necrosome), TRADD Plasma membrane rupture, Cytoplasmic and organelle swelling, Moderate chromatin condensation Intracellular content, DAMPs (e.g., IL-1α, IL-33, IL-6, HSPs) Mostly pro-inflammatory. Anti-inflammatory in certain cases
Ferroptosis (PCD) ROS from iron accumulation and lipid peroxidation GPX4, System XC, GSH, ACSL4 No plasma membrane blebbing or rupture, Small mitochondria with ruptured outer membrane, Normal nucleus DAMPs (e.g., HMGB1, dsDNA), lipid oxidization products (e.g., 4-HNE, LTB4) Pro-inflammatory
Necrosis (Accidental) Microbial infection, Toxins, Trauma, Ischemia, Thermal stress Unspecific Plasma membrane rupture, Cytoplasmic and organelle swelling, Random DNA degradation Intracellular content, DAMPs (e.g., IL-1α, IL-33, dsDNA, ATP, HMGB1) Pro-inflammatory
  1. ACSL4, Acyl-CoA synthetase long-chain family member 4; Bcl-2, B-cell lymphoma 2; DAMPs, danger-associated molecular patterns; dsDNA, double-stranded DNA; GPX4, glutathione peroxidase 4; GSDM, gasdermin; GSH, glutathione; HMGB1, high-mobility group box protein 1; HSPs, heat shock proteins; IL, interleukin; LTB4, Leukotriene B4; MLKL, mixed lineage kinase domain-like protein; PAMPs, pathogen-associated molecular patterns; PCD, programmed cell death; RIPK1/3, receptor-interacting serine/threonine-protein kinase 1/3; ROS, reactive oxygen species; TNF-α, tumor necrosis factor-alpha; TRADD, TNFR-associated death protein; TRAIL, TNF-related apoptosis-inducing ligand; XC, cysteine/glutamate transporter receptor; 4-HNE, 4-Hydroxynonenal