TABLE 2.

The biological function of DAMPs released after solid cancer surgeries

Name	Category	Type	The PPR	Immunity‐related biological function	Reference
HMGB1	Proteins	Nonhistone chromatin nuclear peptide	TLRs 2, 4, 9 and RAGE	The increase in HMGB1 levels after surgery related with the decrease in HLA‐DR expression.	27
Interleukin‐1		Cytokines (IL‐1α and IL‐1β)	IL‐1R	Induce signaling cascades in target cells via MAPK or NF‐κB pathways.	28
Interleukin‐33		Nuclear alarmin	IL‐1RL1	Initiating the potential signaling pathway via NF‐κB and MyD88.	29
S100A proteins		Low molecular weight calcium‐binding homodimeric proteins	RAGE, TLR4	Activated p38 MAPK, ERK1/2, and transcription factor NF‐κB.	30
Histones		Epigenetic regulator	TLR2, TLR4 or TLR9	Extracellular histones induce multiple organ injury via direct endothelia disruption, and the subsequent release of other DAMPs.	31, 32
Complement factors		Effector arm of humoral immunity	Complement receptor	Activation of complement in trauma patients correlate with disease severity.	33, 34, 35
Heat shock proteins		Molecular chaperones	TLR2 and 4	HSP70 can stimulate monocytes/macrophages, and dendritic cells via TLR 2‐ and 4‐ pathways.	27
Nucleic acids	Nonproteins	Nuclear DNA, RNA	TLR3, TLR7, TLR8, TLR9, RAGE	Significantly increased in the immediate posttrauma period.	36, 37
Adenosine triphosphate		Metabolic DAMPs	Purinergic receptor P2 × 7	Contributing to the induction of inflammation by activation and recruitment macrophages, neutrophils, and dendritic cells.	38
Extracellular vesicles		Proteins, mRNAs, miRNAs, lipids	Cell‐to‐cell communicators	A significant increase in plasma extracellular vesicles after traumatic injury had proinflammatory effects that may influence outcomes.	39
Purine metabolites		Uric acid		Uric acid crystals act via inflammasomes, resulting in the production of active proinflammatory cytokines IL‐1β and IL‐18 and neutrophilic influx.	40
Biglycan and Hyaluronic acid		Extracellular matrix	TLR2, TLR4, NLRP3	Induce the secretion of TNF‐α, MIP‐1, and IL‐1β.	41
Succinate	Mitochondrial contents		Succinate receptor	Triggers pro inflammatory differentiation of lymphocytes.	42
Formyl peptides		Nucleoproteins	FP	Extracellular formyl peptides act as neutrophil attractants via FP receptors.	43
mtDNA			TLR9	Promote NLRP3 inflammasome activation, acute pulmonary inflammation, and injury through TLR9, p38 MAPK, and NF‐κB pathways.	44
TFAM		Mitochondrial transcription factor A	RAGE	Guides the TFAM‐mtDNA complexes to the endosomal pathways.	42