Table 2

ICD induction by porphyrin photosensitizers (PSs) of the first generation and second generation (tetrapyrrole PS)

PSSubcellular localization of PSCell lineMarkers of cell death and cell death typesDAMPs expressionImmunogenicity of cancer cells in vitroImmunogenicity of cancer cells in vivoReferences
PhotofrinMitochondria; cellular membranesCT26 murine colon carcinomaApoptosis and necrosis (DNA fragmentation analysis by TUNEL in situ)Surface exposure of HSP27, HSP34,
HSP60, HSP72/73, HSP90, GRP78; no surface exposure of HSP70 or GRP94
Stimulation of IL-12 production by DCsInoculation of DCs into PDT-treated CT26 tumors growing in BALB/c mice stimulated cytotoxic activity in lymph node and spleen.
Spleen lymphocytes produced TNF
73
SCCVII murine squamous cell carcinoma (SCC)Apoptosis (flow cytometry: caspase three active form)Surface exposure of HSP70, HSP60, GRP94; release of HSP70; no surface exposure of GRP78HSP70 and GRP94 exposure on the macrophages surface, production of TNF-α and NF-κBPDT-treated SCCVII tumors growing in C3H/HeN mice: surface exposure of HSP70 on leukocytes, and HSP60 and GRP94 on tumor-associated neutrophils and macrophages74
LLC murine lung carcinoma (Lewis lung carcinoma)N/DSurface exposure of CRT (in vitro and in vivo);
HMGB1 levels in serum
↑ levels of intracellular HMGB1 in macrophages co-incubated with PDT-treated LLC cellsPDT-treated LLC tumors growing in syngeneic C57BL/6 mice: exposure of CRT on the surface of tumor-associated macrophages60
Protoporphyrin IX (PpIX) induced by exogenic 5-aminolevulinic acidMitochondriaGL261 murine gliomaApoptosis (PtdSer exposure)Surface exposure of HSP70; release of ATPN/DN/D70
U87 human glioblastoma, U251 human glioblastoma, astrocytomaApoptosis (DNA fragmentation analysis by TUNEL staining)Surface exposure of HSP70Phenotypic maturation of DCs (CD40high, CD80high, CD83high, CD86high)N/D88
PECA murine SCCApoptosis and necrosis (PtdSer exposure with a vital dye staining)N/DPhenotypic maturation of DCs (CD80high, CD86high, MHC IIhigh), production of IFN-γ and IL-12Prophylactic PDT-DC-based vaccination model in SKH-1 mice136
PECA murine SSCApoptosis (DNA fragmentation analysis by TUNEL staining)Surface exposure of CRT and HSP70; release of HMGB1 and HSP70 in PECA cells (in vitro and in vivo)Phenotypic maturation of DCs (CD80high, CD86high, MHC IIhigh), production of IFN-γ and IL-12Prophylactic vaccination model using ALA-PDT-treated SCC cells in SKH-1 mice75
PpIX induced by endogenic 5-methylaminolevulinic acidERB16-OVA murine melanomaApoptosis (PtdSer exposure)Surface exposure of CRT; enhanced expression of INF-1Phenotypic maturation of DCs (CD86high, MHC IIhigh)N/D87
Meso-tetrahydroxyphenyl chlorinEREMT6 murine mammary carcinomaN/DSurface exposure and release of HSP70 (in vitro and in vivo)N/DN/D72
SCCVII murine SCCN/DN/DN/DPDT-treated SCCVII tumors growing in C3H/HeN mice: rapid blood neutrophils137
Glycoconjugated chlorin (G-chlorin)MitochondriaCT26 murine colon carcinomaApoptosis (flow cytometry: caspase three active form)Surface exposure of CRT and release of HMGB1 (in vitro and in vivo)N/DProphylactic vaccination model using G-chlorin-PDT-treated CT26 cells in BALB/c mice61
PhotodithazineER and Golgi apparatusGL261 murine glioma, MCA205 murine sarcomaApoptosis in GL261 (inhibitors analysis, PtdSer exposure with a vital dye staining)Surface exposure of CRT; release of ATP and HMGB1Phenotypic maturation of DCs (CD40high, CD86high, MHC IIhigh), production of IL-6Prophylactic vaccination model using photodithazine-PDT-treated MCA205 cells in immunocompetent C57BL/6J mice46
PhotosensLysosomesGL261 murine glioma, MCA205 murine sarcomaApoptosis and ferroptosis in GL261 (inhibitors analysis, PtdSer exposure with a vital dye staining)Surface exposure of CRT; release of ATP and HMGB1Phenotypic maturation of DCs (CD40high, CD86high, MHC IIhigh), production of IL-6Prophylactic vaccination model using Photosens-PDT-treated MCA205 cells in immunocompetent C57BL/6J mice46
2-[1-Hexyloxyethyl]-2-devinyl pyropheophorbide (HPPH)MitochondriaColon26-HA murine colorectal carcinoma, 4T1 murine mammary carcinomaApoptosis (caspase-3 activity and TUNEL assay138)N/DN/DTumor-bearing BALB/c mice that remained tumor free after the treatment were challenged with Colo26 or 4T1 cells.
(A tumor-controlling PDT regimen was combined with an immune-enhancing PDT regimen)
89
Sodium Porfimer (Photofrin)
Hydrophilic bacteriochlorin (F2BOH)N/DCT26 murine colorectal carcinomaApoptosis and necrosis (PtdSer exposure with a vital dye staining)N/DN/DPDT-F2BOH cured CT26 tumor-bearing BALB/c mice rejected tumor re-inoculation 1 year after the treatment139
  • CD, cluster of differentiation; CRT, calreticulin; DC, dendritic cell; ER, endoplasmic reticulum; GRP, glucose-regulated protein; HMGB1, high-mobility group protein box 1; HSP, heat shock protein; IFN, interferon; IL, interleukin; MHC, major histocompatibility complex; N/D, not detected; NF-κB, nuclear factor kappa-light-chain-enhancer of activated B; PDT, photodynamic therapy; PtdSer, phosphatidylserine; TNF, tumor necrosis factor; TUNEL, terminal deoxynucleotidyl transferase-mediated nick end labeling analysis.