Table 1

ICD induction by non-porphyrin photosensitizers

PS	Subcellular localization of PS	Cell line	Markers of cell death and cell death types	Mode of DAMPs release/exposure	Immunogenicity of cancer cells in vitro	Immunogenicity of cancer cells in vivo	References
Hypericin	ER	T24 human bladder carcinoma	N/D	Surface exposure of HSP70 and CRT; no surface exposure of HSP90	N/D	N/D	66
		T24 human bladder carcinoma	Apoptosis (PtdSer exposure)	Surface exposure of CRT; No surface exposure of HSP90; release of ATP, CRT, HSP90, and HSP70	Phenotypic maturation of DCs (CD80^high, CD83^high, CD86^high, MHC II^high) and functional stimulation (NO^high, IL-10^absent, IL-1β^high)	N/D	43
		CT26 murine colon carcinoma	Apoptosis (WB: caspase-3 and PARP cleavage)	Surface exposure of CRT; release of ATP	N/D	Prophylactic vaccination model using hypericin-PDT-treated CT26 cells in immunocompetent BALB/c mice	43
		GL261 murine glioma	Apoptosis (WB: caspase-3 cleavage)	Surface exposure of CRT, HSP70 and HSP90; release of HMGB1 and ATP	Phenotypic maturation of DCs (CD80^high, CD86^high, CD40^high, MHC I^high)	Prophylactic PDT-based DC vaccination model in immunocompetent, syngeneic C57BL/6 mice: ↑ brain infiltration by CD3⁺ T-lymphocytes, CD4⁺ and CD8⁺ T-lymphocytes, T_H1 cells, CTLs and T_H17 cells. Splenocytic T cells showed significantly higher IFN-γ production on restimulation with GL261 cells	70
OR141	ER	SCC7 murine head and neck carcinoma, A431 human epidermoid carcinoma	Necrosis and late apoptosis (WB: PARP cleavage, PtdSer exposure with a vital dye staining)	Surface exposure of CRT; release of HSP90, annexin A1, HMGB1 and ATP	Phenotypic maturation of DCs (CD80^high, CD86^high, MHC II^high)	Therapeutic vaccination model in C3H/HeNRj mice: PDT-based DC vaccination more effective than PDT-killed SCC7 cells vaccination. CD8⁺ inﬁltration in PDT-treated tumors	52
OR141	ER	Ab1, Ab12 murine mesothelioma	N/D	Surface exposure of CRT; release of HSP90 and HMGB1	Phenotypic maturation of DCs (CD80^high, CD86^high, CD40^high, MHC II^high)	Therapeutic PDT-based DC vaccination model in BALB/c mice (Ab1 cells): ↑ infiltration with CD8⁺ T-lymphocytes, and INF-γ in tumor. ↑ migration potential of DCs primed with OR141-killed mesothelioma cells. ↑ CD8⁺ and CD4+T cells in splenocytes, ↑ IFN-γ production (IFN-γ positive CD8⁺ population) when re-exposed to Ab1	71
8-Methoxypsoralen (8-MOP), extracorporeal photochemotherapy 8-MOP, extracorporeal photochemotherapy	N/D	YUMM1.7 murine melanoma, MC38 murine colon adenocarcinoma	Apoptosis (APO2-PE, trypan blue, and/or PtdSer and PI staining135)	N/D	Phenotypic maturation of DCs (CD80^high, CD83^high, CD86^high, MHC II^high, HLA-DR^high) TI protocol using human PBMC: DCs activation and maturation (surface upregulation of the HLA-DR, CD80, CD83, and CD86), monocytes activation (↑ ICAM-1, PLAUR and CCL2+ cells)	Therapeutic vaccination model using mixture of PBMCs incubated with PDT-treated tumor cells in tumor-bearing C57BL/6J mice. Depletion of CD4 T cells, CD8 T cells and NK1.1+ cells in YUMM1.7-bearing mice diminished the antitumor effect of TI treatment. Prophylactic vaccination model using isolated splenocytes or enriched splenic T cells from TI-treated YUMM1.7-bearing mice	83 135
		B16 murine melanoma expressing ovalbumin (B16-OVA), YUMMER murine melanoma, MC38 murine colon adenocarcinoma	Apoptosis (PtdSer exposure)	Surface exposure of CRT, release of ATP and HMGB1 (in B16-OVA cells)	Treated B16-OVA cells efficiently engulfed by monocytes to drive the cross-priming of tumor-specific CD8⁺ lymphocytes	Prophylactic vaccination model using 8-MOP-PDT-treated B16-OVA, YUMMER and MC38 cells in immunocompetent C57BL/6 mice	82
		Activated alloreactive T cells in vitro, peripheral blood mononuclear cells from GVHD patients	Apoptosis (PtdSer exposure)	Surface exposure of CRT, release of HMGB1. No release of ATP	Treated cells efficiently engulfed by macrophages and DC differentiated from monocytes. Absence of phenotypic maturation of DCs (CD80^low, CD40^low) and absence of IL-12, IL-6 and IFN-γ secretion by DCs. No ability to stimulate and polarize naive T cells by DCs	N/D	84
Rose Bengal acetate	Cytoskeleton; mitochondria; Golgi apparatus; ER	HeLa human cervical carcinoma	Apoptosis and autophagy (staining for PtdSer exposure and MDC)	Surface exposure of CRT, HSP70 and HSP90 on apoptotic cells; exposure of HSP70 and HSP90 on autophagic cells; release of HSP70, HSP90, ATP (only by apoptotic cells) and HMGB1 (by secondary necrotic cells)	N/D	N/D	65

ATP, adenosine triphosphate; CD, cluster of differentiation; CRT, calreticulin; DC, dendritic cell; ER, endoplasmic reticulum; GVHD, graft versus host disease; HLA, human leukocyte antigen; HMGB1, high-mobility group protein box 1; HSP, heat shock protein; ICAM-1, intercellular adhesion molecule 1; IFN, interferon; IL, interleukin; MDC, monodansylcadaverine; MHC, major histocompatibility complex; N/D, not detected; NK, natural killer; NO, nitric oxide; PARP, poly ADP ribose polymerase; PBMC, platelet-containing peripheral blood mononuclear cell; PDT, photodynamic therapy; PI, propidium iodide; PLAUR, urokinase plasminogen activator surface receptor; PS, photosensitizer; PtdSer, phosphatidylserine; TI, transimmunization; WB, western blot analysis.