Table 1

ICD induction by non-porphyrin photosensitizers

PSSubcellular localization of PSCell lineMarkers of cell death and cell death typesMode of DAMPs release/exposureImmunogenicity of cancer cells in vitroImmunogenicity of cancer cells in vivoReferences
HypericinERT24 human bladder carcinomaN/DSurface exposure of HSP70 and CRT; no surface exposure of HSP90N/DN/D66
T24 human bladder carcinomaApoptosis (PtdSer exposure)Surface exposure of CRT;
No surface exposure of HSP90; release of ATP, CRT, HSP90, and HSP70
Phenotypic maturation of DCs (CD80high, CD83high, CD86high, MHC IIhigh) and functional stimulation (NOhigh, IL-10absent, IL-1βhigh)N/D43
CT26 murine colon carcinomaApoptosis (WB: caspase-3 and PARP cleavage)Surface exposure of CRT; release of ATPN/DProphylactic vaccination model using hypericin-PDT-treated CT26 cells in immunocompetent BALB/c mice
GL261 murine gliomaApoptosis (WB: caspase-3 cleavage)Surface exposure of CRT, HSP70 and HSP90; release of HMGB1 and ATPPhenotypic maturation of DCs (CD80high, CD86high, CD40high, MHC Ihigh)Prophylactic PDT-based DC vaccination model in immunocompetent, syngeneic C57BL/6 mice:
brain infiltration by CD3+ T-lymphocytes, CD4+ and CD8+ T-lymphocytes, TH1 cells, CTLs and TH17 cells.
Splenocytic T cells showed significantly higher IFN-γ production on restimulation with GL261 cells
OR141ERSCC7 murine head and neck carcinoma, A431 human epidermoid carcinomaNecrosis and late apoptosis (WB: PARP cleavage, PtdSer exposure with a vital dye staining)Surface exposure of CRT; release of HSP90, annexin A1, HMGB1 and ATPPhenotypic maturation of DCs (CD80high, CD86high, MHC IIhigh)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
Ab1, Ab12 murine mesotheliomaN/DSurface exposure of CRT; release of HSP90 and HMGB1Phenotypic maturation of DCs (CD80high, CD86high, CD40high, MHC IIhigh)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
8-Methoxypsoralen (8-MOP), extracorporeal photochemotherapy
8-MOP, extracorporeal photochemotherapy
N/DYUMM1.7 murine melanoma, MC38 murine colon adenocarcinomaApoptosis (APO2-PE, trypan blue, and/or PtdSer and PI staining135)N/DPhenotypic maturation of DCs (CD80high, CD83high, CD86high, MHC IIhigh, HLA-DRhigh)
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 adenocarcinomaApoptosis (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+ lymphocytesProphylactic vaccination model using 8-MOP-PDT-treated B16-OVA, YUMMER and MC38 cells in immunocompetent C57BL/6 mice82
Activated alloreactive T cells in vitro, peripheral blood mononuclear cells from GVHD patientsApoptosis (PtdSer exposure)Surface exposure of CRT, release of HMGB1. No release of ATPTreated cells efficiently engulfed by macrophages and DC differentiated from monocytes. Absence of phenotypic maturation of DCs (CD80low, CD40low) and absence of IL-12, IL-6 and IFN-γ secretion by DCs. No ability to stimulate and polarize naive T cells by DCsN/D84
Rose Bengal acetateCytoskeleton; mitochondria;
Golgi apparatus;
HeLa human cervical carcinomaApoptosis 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/DN/D65
  • 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.