Photodynamic therapy and anti-tumor immunity.
OBJECTIVE
Photodynamic therapy (PDT) efficacy appears to be enhanced in the presence of an intact immune system and PDT has been shown to augment anti-tumor immunity. The mechanisms leading to the enhancement of the host immune response to tumor are unclear. Anti-tumor immunity depends upon the presence of activated antigen presenting cells (APCs). These cells are activated by their recognition of components released by pathogens, viruses, dead cells, and the presence of pro-inflammatory mediators. Activated APCs stimulate the generation of cytokine secreting effector cells. Therefore, we have hypothesized that PDT generated inflammatory mediators and components released from tumor cells killed by PDT results in the activation of APCs capable of stimulating effector T-cell proliferation and cytokine secretion.


METHODS
To determine the effect of PDT on APCs, tumor draining lymph nodes (TDLNs) of EMT6 or Colo 26 tumor bearing mice were isolated 24 hours after Photofrin-PDT and flow cytometry was used to detect the presence of APCs secreting the T cells stimulatory cytokine, IL-12. APCs were also isolated from TDLNs and used to stimulate T-cell proliferation and secretion of interferon-gamma (IFN-gamma).


RESULTS
PDT results in an increase in IL-12 expressing APCs in the TDLN. This increase was accompanied by an increase in the ability of APCs isolated from TDLNs of PDT-treated mice to stimulate T-cell proliferation and T-cell secretion of IFN-gamma.


CONCLUSIONS
Our results indicate that APCs isolated from PDT-treated mice exhibit an enhanced ability to stimulate T-cell proliferation and IFN-gamma secretion, suggesting that PDT results in increased APC activity.
Gollnick
Sandra O
SO
The Photodynamic Therapy Center, Department of Cell Stress Biology, Roswell Park Cancer Institute, Buffalo, New York 14263, USA. Sandra.Gollnick@roswellpark.org
Owczarczak
Barbara
B
Maier
Patricia
P
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D017323:Dihematoporphyrin Ether / Q000494:pharmacology; D005434:Flow Cytometry; D007371:Interferon-gamma / Q000378:metabolism*; D018664:Interleukin-12 / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D009374:Neoplasms, Experimental / Q000188:drug therapy / Q000276:immunology; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000494:pharmacology; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism
D017319:Photosensitizing Agents; D018664:Interleukin-12; D007371:Interferon-gamma; D017323:Dihematoporphyrin Ether