Immune response after photodynamic therapy increases anti-cancer and anti-bacterial effects

Table 2 Damage-associated molecular pattern molecules that may be released or exposed on the outer leaflet of dying tumor cells after photodynamic therapy

DAMP	Function	Ref.
HSP60, HSP70, HSP90, gp96, GRP94, GRP78	Molecular chaperones that normally reside in intracellular regions/organelles, but under stress they are exposed on the damaged cell surface and prime immunomodulatory processes	[11,21,22,112]
Calreticulin	Calcium binding protein located in intracellular regions/organelles (mostly in ER), but under stress its presence on the PM is augmented. On the PM it acts as “danger signal” and increases the immunogenicity of the dying cells	[11,112]
ATP	High-energy molecule, normally intracellular, but can be released by necrotic and apoptotic cells under particular stresses. Extracellular ATP has the ability to help in chemoattraction of immune cells	[12,112]
Phosphatidylserine	When cells are damaged/dying, phosphatidylserine is transposed from the inner to the outer leaflet and acts as an “eat me” signal by interacting with multiple immune cells receptors, mediating efficient phagocytosis and anti-inflammatory responses	[112,113]
High mobility group box-1	Nuclear chromatin-binding protein; it has prominent cytokine-line properties and when released by dying cells tends to stimulate immune cells to produce various pro-inflammatory cytokines	[11,112]
Calgranulin family members (S100A8, S100A9, S100A12)	Calcium-binding proteins; when released by necrotic cells they act as “find me” signals attracting various immune cells and interacting with immune cell receptor (TLR4/RAGE) to induce the secretion of pro-inflammatory cytokines	[11,112,114]
Cross-linked dimer of ribosomal protein S19	Constituent of small ribosomal subunit; when released by necrotic cells it acts as a chemotactic factor for attracting various immune cells	[11,112]

DAMPs: Damage-associated molecular patterns; ER: Endoplasmatic reticulum; PM: Plasma membrane; HSP: Heat shock protein; GRP: Glucose-regulated protein; ATP: Adenosine triphosphate; TLR4: Toll-like receptor 4; RAGE: Receptor for advanced glycation end-products.