Table 1. Comparison of multiple forms of programmed cell death and necrosis.

	Apoptosis (type 1 PCD)	Autophagic cell death (type 2 PCD)	Necroptosis (type 3 PCD)	Pyroptosis	Necrosis
Mode of cell death	Programmed	Programmed	Programmed	Programmed	Accidental
Initiators	TNF-α, FasL, or TRAIL, infectious pathogens	Nutrient deprivation, HDAC inhibitors, hypoxia, infectious pathogens	TNF-α, FasL, or TRAIL, microbial infections Ischemic injury	DAMPs, microbial infections	Toxins, infections, inflammation, trauma
Intermediate signalings	Mitochondrial pathway Caspase-3, -6, -7-dependent	Caspase-independent autophagosome formation Lysosomal protease	TNF receptor signaling JNK activation Caspase-independent RIP1/RIP3 necrosome	Nod-like receptors Caspase 1-dependent pyroptosome Inflammasome	-
Terminal cellular events	Non-lytic cell shrinkage DNA fragmentation apoptotic bodies	Non-lytic autophagic bodies	Non-lytic, loss of plasma membrane, swollen cellular organelles	Lytic, rapid loss of plasma membrane, cell swelling, pore formation	Lytic, plasma membrane rupture, leak of content
Inflammation	Non-inflammatory	Non-inflammatory	Proinflammatory	Proinflammatory	Proinflammatory
Immunogenicity	+	+	++	++	+++
DAMPs released	Ecto-CRT HMGB1 and ATP release	HMGB1 and ATP release	Long genomic DNA IL-6	HMGB1 and ATP release IL-1α, IL-1β, IL-6, IL-18, and TNF-α chemokines	HMGB1 and ATP release IL-1α, IL-33 mRNA, and genomic DNA
Eat-me signals	Ecto-CRT	LPC secretion PS exposure	LPC secretion PS exposure	PS exposure	PS exposure

Abbreviations: TNF-α, tumor necrosis factor- α; FasL, Fas ligand; TRAIL, TNF-related apoptosis-inducing ligand; HDAC, histone deacetylase; IL-1α, interleukin-1α ; IL-1β, interleukin-1β; IL-6, interleukin-6; IL-18, interleukin-18; IL-33, interleukin-33; ICD, immunogenic cell death; LPC, lysophosphatidylcholine; PS, phosphatidylserine; JNK, c-Jun N-terminal kinase.

The table gives a schematic overview of the multiple forms of cell death incuding apoptotic cell death (type 1 PCD), autophagic cell death (type 2 PCD), cell death induced by necroptosis (type 3 PCD), pyroptosis and necrosis. The extent of immunogenicity in each cell death subsection is scored as +, ++, and +++, according to the expression levels of ‘eat-me' signals and DAMPs emission. ICD in cancer can display different ‘eat-me' signals, including ecto-CRT and LPC, on the cell membrane, as well as emission of DAMPs, ATP, and HMGB1. This peculiar ecto-CRT, which facilitates engulfment of TAAs from cancer cells by DCs, can only be found on cells that succumb to immunogenic apoptosis, whereas it is not present on cells dying in an immunologically silent manner. LPC secretion, PS exposure, and ATP release require autophagy induction. Numerous exquisite expression patterns shaped by the constituents of DAMPs and the interactive status of the immune system will predominantly determine the fate of subsequent immune responses, namely, immune tolerance or antitumor immunity