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Review
. 2011 May;10(5):751-8.
doi: 10.1039/c0pp00345j. Epub 2011 Mar 24.

The immunosuppressive side of PDT

Pawel Mroz  1 , Michael R Hamblin
Affiliations
Review

The immunosuppressive side of PDT

Pawel Mroz et al. Photochem Photobiol Sci. 2011 May.

Abstract

Photodynamic therapy (PDT) is a promising novel therapeutic procedure for the management of a variety of solid tumors and many non-malignant diseases. PDT has been described as having a significant effect on the immune system, which may be either immunostimulatory or, in some circumstances, immunosuppressive. The immunosuppressive effects of PDT have nearly all been concerned with the suppression of the contact hypersensitivity reaction in mice. Here, we review the immunosuppressive aspects of PDT treatment and discuss some additional mechanisms that may be involved.

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Figures

Fig. 1
Fig. 1
Potential mechanism that involved in PDT-mediated local and systemic immunosuppression. PDT tissue damage leads to release of various antigens that elicit activation of immune and regulatory responses. The local activation of the immune response after PDT may lead to DC translocation to the regional lymph nodes (LN) and subsequent presentation of antigens to naïve T cells. However, this activation may trigger counteraction that leads to the suppression of PDT-mediated immunity. The DC may not only deliver the antigen to LN in a stimulatory way but also in a tolerogenic manner. The activated T cells may be on the other hand prevented from functioning by T regulatory cells or immunosuppressive cytokines that may be locally secreted in the response to PDT insult and resulting inflammation. Tregs may also be responsible for observed systemic PDT effects. APC – antigen presenting cells, DC – dendritic cells.
Fig. 2
Fig. 2
Potential mechanisms of tolerance induction by PDT of tumors. PDT of tumor cells leads to apoptotic cell death that may release DAMPs, however ROS produced during PDT may inactivate the immunostimulatory potential of these molecules. Apoptotic cells may also release immunosuppressive cytokines like IL-10 or TGFβ or stimulate macrophages to release them. Immunosuppressive cytokines may in turn change CD4+ T cells into inducible Treg cells, while the lack of CD4+ T cell co-stimulation will result in generation of anergic CD8+ T cells. Additionally, high levels of VEGF released during PDT may affect the maturation of DC resulting in creating highly tolerogenic and immunosuppressive environment. Mφ – macrophages, DC – dendritic cells, iDC – immature dendritic cells, ROS – reactive oxygen species, DAMP – damage activated molecular pattern, VEGF – vascular endothelial growth factor, TGFβ – transforming growth factor β.
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