Effective photoimmunotherapy of murine colon carcinoma induced by the combination of photodynamic therapy and dendritic cells

Clin Cancer Res. 2004 Jul 1;10(13):4498-508. doi: 10.1158/1078-0432.CCR-04-0367.

Abstract

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 (IL)-12 was measured with ELISA. Cytotoxic activity of lymph node cells was evaluated in a standard (51)Cr-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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis
  • Blotting, Western
  • Bone Marrow Cells / cytology
  • Cell Line, Tumor
  • Cell Movement
  • Chaperonin 60 / metabolism
  • Chromium Radioisotopes
  • Coculture Techniques
  • Colonic Neoplasms / therapy*
  • DNA Fragmentation
  • Dendritic Cells / cytology*
  • Dendritic Cells / metabolism
  • Endocytosis
  • Enzyme-Linked Immunosorbent Assay
  • Flow Cytometry
  • HSC70 Heat-Shock Proteins
  • HSP70 Heat-Shock Proteins / metabolism
  • HSP72 Heat-Shock Proteins
  • HSP90 Heat-Shock Proteins / metabolism
  • Heat-Shock Proteins / metabolism
  • Heme Oxygenase (Decyclizing) / metabolism
  • Heme Oxygenase-1
  • Humans
  • In Situ Nick-End Labeling
  • Inflammation
  • Intracellular Signaling Peptides and Proteins
  • Lymphatic Metastasis
  • Membrane Proteins
  • Mice
  • Mice, Inbred BALB C
  • Microscopy, Confocal
  • Molecular Chaperones / metabolism
  • Necrosis
  • Photochemotherapy*
  • Protein-Serine-Threonine Kinases / metabolism
  • T-Lymphocytes / metabolism
  • Time Factors

Substances

  • Chaperonin 60
  • Chromium Radioisotopes
  • HSC70 Heat-Shock Proteins
  • HSP70 Heat-Shock Proteins
  • HSP72 Heat-Shock Proteins
  • HSP90 Heat-Shock Proteins
  • HSPA8 protein, human
  • Heat-Shock Proteins
  • Hspa8 protein, mouse
  • Intracellular Signaling Peptides and Proteins
  • Membrane Proteins
  • Molecular Chaperones
  • HMOX1 protein, human
  • Heme Oxygenase (Decyclizing)
  • Heme Oxygenase-1
  • Hmox1 protein, mouse
  • MAP-kinase-activated kinase 2
  • Protein-Serine-Threonine Kinases
  • molecular chaperone GRP78