Stimulation of dendritic cells enhances immune response after photodynamic therapy
Name
Mroz-2009-Stimulation of dendritic cells enhances immune response after photodynamic therapy.pdf
Size
604.15 KB
Format
Adobe PDF
Checksum (MD5)
1c8e75768115cd3dcc2e82266482cf5b
Author(s)
Mroz, Pawel
Castano, Ana P.
Hamblin, Michael R.
Date Issued
January 2009
Journal
Biophotonics and Immune Responses IV
Publisher
Society of Photo-optical Instrumentation Engineers
Citation
Mroz, Pawel, Ana P. Castano, and Michael R. Hamblin. “Stimulation of dendritic cells enhances immune response after photodynamic therapy.” Biophotonics and Immune Responses IV. Ed. Wei R. Chen. San Jose, CA, USA: SPIE, 2009. 717803-10. © 2009 Society of Photo-optical Instrumentation Engineers.
Version
Final published version
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 nave 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.
MIT Department
Harvard University--MIT Division of Health Sciences and Technology
Terms of Use
Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.
Persistent DSpace Link
DOI of Published Version
http://dx.doi.org/10.1117/12.809630
