TY - JOUR
T1 - Effective photoimmunotherapy of murine colon carcinoma induced by the combination of photodynamic therapy and dendritic cells
AU - Jalili, Ahmad
AU - Makowski, Marcin
AU - Świtaj, Tomasz
AU - Nowis, Dominika
AU - Wilczyński, Grzegorz M.
AU - Wilczek, Ewa
AU - Chora̧zy-Massalska, Magdalena
AU - Radzikowska, Anna
AU - Maśliński, Włodzimierz
AU - Białly, Łukasz
AU - Sieńko, Jacek
AU - Sieroń, Aleksander
AU - Adamek, Mariusz
AU - Basak, Grzegorz
AU - Mróz, Paweł
AU - Krasnodȩbski, Ireneusz W.
AU - Jakóbisiak, Marek
AU - Goła̧b, Jakub
PY - 2004/7/1
Y1 - 2004/7/1
N2 - Purpose: The unique mechanism of tumor destruction by photodynamic therapy (PDT), resulting from apoptotic and necrotic killing of tumor cells accompanied by local inflammatory reaction and induction of heat shock proteins (HSPs), prompted us to investigate the antitumor effectiveness of the combination of PDT with administration of immature dendritic cells (DCs). Experimental Design: Confocal microscopy and Western blotting were used to investigate the influence of PDT on the induction of apoptosis and expression of HSP expression in C-26 cells. Confocal microscopy and flow cytometry studies were used to examine phagocytosis of PDT-treated C-26 cells by DCs. Secretion of interleukin (ILL)-12 was measured with ELISA. Cytotoxic activity of lymph node cells was evaluated in a standard 51Cr-release assay. The antitumor effectiveness of PDT in combination with administration of DCs was investigated in in vivo model. Results: PDT treatment resulted in the induction of apoptotic and necrotic cell death and expression of HSP27, HSP60, HSP72/73, HSP90, HO-1, and GRP78 in C-26 cells. Immature DCs cocultured with PDT-treated C-26 cells efficiently engulfed killed tumor cells, acquired functional features of maturation, and produced substantial amounts of IL-12. Inoculation of immature DCs into the PDT-treated tumors resulted in effective homing to regional and peripheral lymph nodes and stimulation of cytotoxic activity of T and natural killer cells. The combination treatment with PDT and administration of DCs produced effective antitumor response. Conclusions: The feasibility and antitumor effectiveness demonstrated in these studies suggest that treatment protocols involving the administration of immature DCs in combination with PDT may have clinical potential.
AB - Purpose: The unique mechanism of tumor destruction by photodynamic therapy (PDT), resulting from apoptotic and necrotic killing of tumor cells accompanied by local inflammatory reaction and induction of heat shock proteins (HSPs), prompted us to investigate the antitumor effectiveness of the combination of PDT with administration of immature dendritic cells (DCs). Experimental Design: Confocal microscopy and Western blotting were used to investigate the influence of PDT on the induction of apoptosis and expression of HSP expression in C-26 cells. Confocal microscopy and flow cytometry studies were used to examine phagocytosis of PDT-treated C-26 cells by DCs. Secretion of interleukin (ILL)-12 was measured with ELISA. Cytotoxic activity of lymph node cells was evaluated in a standard 51Cr-release assay. The antitumor effectiveness of PDT in combination with administration of DCs was investigated in in vivo model. Results: PDT treatment resulted in the induction of apoptotic and necrotic cell death and expression of HSP27, HSP60, HSP72/73, HSP90, HO-1, and GRP78 in C-26 cells. Immature DCs cocultured with PDT-treated C-26 cells efficiently engulfed killed tumor cells, acquired functional features of maturation, and produced substantial amounts of IL-12. Inoculation of immature DCs into the PDT-treated tumors resulted in effective homing to regional and peripheral lymph nodes and stimulation of cytotoxic activity of T and natural killer cells. The combination treatment with PDT and administration of DCs produced effective antitumor response. Conclusions: The feasibility and antitumor effectiveness demonstrated in these studies suggest that treatment protocols involving the administration of immature DCs in combination with PDT may have clinical potential.
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U2 - 10.1158/1078-0432.CCR-04-0367
DO - 10.1158/1078-0432.CCR-04-0367
M3 - Article
C2 - 15240542
AN - SCOPUS:3042770952
SN - 1078-0432
VL - 10
SP - 4498
EP - 4508
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 13
ER -