Stimulation of dendritic cells enhances immune response after photodynamic therapy

Pawel Mroz, Ana P. Castano, Michael R. Hamblin

Research output: Contribution to journalConference article

1 Citation (Scopus)

Abstract

Photodynamic therapy (PDT) involves the administration of photosensitizers followed by illumination of the primary tumor with red light producing reactive oxygen species that cause vascular shutdown and tumor cell necrosis and apoptosis. Anti-tumor immunity is stimulated after PDT due to the acute inflammatory response, priming of the immune system to recognize tumor-associated antigens (TAA). The induction of specific CD8+ Tlymphocyte cells that recognize major histocompatibility complex class I (MHC-I) restricted epitopes of TAAs is a highly desirable goal in cancer therapy. The PDT killed tumor cells may be phagocytosed by dendritic cells (DC) that then migrate to draining lymph nodes and prime naïve T-cells that recognize TAA epitopes. This process is however, often sub-optimal, in part due to tumor-induced DC dysfunction. Instead of DC that can become mature and activated and have a potent antigen-presenting and immune stimulating phenotype, immature dendritic cells (iDC) are often found in tumors and are part of an immunosuppressive milieu including regulatory T-cells and immunosuppressive cytokines such as TGF-beta and IL10. We here report on the use of a potent DC activating agent, an oligonucleotide (ODN) that contains a non-methylated CpG motif and acts as an agonist of toll like receptor (TLR) 9. TLR activation is a danger signal to notify the immune system of the presence of invading pathogens. CpG-ODN (but not scrambled non-CpG ODN) increased bone-marrow DC activation after exposure to PDT-killed tumor cells, and significantly increased tumor response to PDT and mouse survival after peri-tumoral administration. CpG may be a valuable immunoadjuvant to PDT especially for tumors that produce DC dysfunction.

Original languageEnglish (US)
Article number717803
JournalProgress in Biomedical Optics and Imaging - Proceedings of SPIE
Volume7178
DOIs
StatePublished - Jun 1 2009
EventBiophotonics and Immune Responses IV - San Jose, CA, United States
Duration: Jan 25 2009Jan 26 2009

Fingerprint

Photodynamic Therapy
Dendritic Cells
Photodynamic therapy
Immune Response
Photochemotherapy
stimulation
Tumors
Tumor
therapy
tumors
cells
Neoplasms
antigens
Antigens
Epitopes
immune systems
Neoplasm Antigens
T-cells
Immunosuppressive Agents
Immune system

Keywords

  • Anti-tumor immunity
  • CpG oligodeoxynucleotide
  • Dendritic cells
  • Photodynamic therapy
  • Toll like receptors

Cite this

Stimulation of dendritic cells enhances immune response after photodynamic therapy. / Mroz, Pawel; Castano, Ana P.; Hamblin, Michael R.

In: Progress in Biomedical Optics and Imaging - Proceedings of SPIE, Vol. 7178, 717803, 01.06.2009.

Research output: Contribution to journalConference article

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abstract = "Photodynamic therapy (PDT) involves the administration of photosensitizers followed by illumination of the primary tumor with red light producing reactive oxygen species that cause vascular shutdown and tumor cell necrosis and apoptosis. Anti-tumor immunity is stimulated after PDT due to the acute inflammatory response, priming of the immune system to recognize tumor-associated antigens (TAA). The induction of specific CD8+ Tlymphocyte cells that recognize major histocompatibility complex class I (MHC-I) restricted epitopes of TAAs is a highly desirable goal in cancer therapy. The PDT killed tumor cells may be phagocytosed by dendritic cells (DC) that then migrate to draining lymph nodes and prime na{\"i}ve T-cells that recognize TAA epitopes. This process is however, often sub-optimal, in part due to tumor-induced DC dysfunction. Instead of DC that can become mature and activated and have a potent antigen-presenting and immune stimulating phenotype, immature dendritic cells (iDC) are often found in tumors and are part of an immunosuppressive milieu including regulatory T-cells and immunosuppressive cytokines such as TGF-beta and IL10. We here report on the use of a potent DC activating agent, an oligonucleotide (ODN) that contains a non-methylated CpG motif and acts as an agonist of toll like receptor (TLR) 9. TLR activation is a danger signal to notify the immune system of the presence of invading pathogens. CpG-ODN (but not scrambled non-CpG ODN) increased bone-marrow DC activation after exposure to PDT-killed tumor cells, and significantly increased tumor response to PDT and mouse survival after peri-tumoral administration. CpG may be a valuable immunoadjuvant to PDT especially for tumors that produce DC dysfunction.",
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