Stimulation of anti-tumor immunity by photodynamic therapy

Abstract

Photodynamic therapy (PDT) is a rapidly developing cancer treatment that utilizes the combination of nontoxic dyes and harmless visible light to destroy tumors by generating reactive oxygen species. PDT produces tumor-cell destruction in the context of acute inflammation that acts as a ‘danger signal’ to the innate immune system. Activation of the innate immune system increases the priming of tumor-specific T lymphocytes that have the ability to recognize and destroy distant tumor cells and, in addition, lead to the development of an immune memory that can combat recurrence of the cancer at a later point in time. PDT may be also successfully combined with immunomodulating strategies that are capable of overcoming or bypassing the escape mechanisms employed by the progressing tumor to evade immune attack. This article will cover the role of the immune response in PDT anti-tumor effectiveness. It will highlight the milestones in the development of PDT-mediated anti-tumor immunity and emphasize the combination strategies that may improve this therapy.

Keywords::

• anti-tumor immunity
• cancer vaccines
• cytotoxic T-lymphocytes
• damage-associated molecular patterns
• dendritic cells
• photodynamic therapy
• Toll-like receptor agonists
• tumor-associated antigens

Acknowledgements

Norbert Lange would like to dedicate his participation to this review to his beloved father.

The authors are grateful to Mladen Korbelik, Jakub Golab and Abhishek Garg for helpful discussions.

Financial & competing interests disclosure

Pawel Mroz was partly supported by Partners Genzyme Translational Grant. Norbert Lange was supported by the Swiss Science Foundation (Grants #205320-122144, #IZLSZ2_123011, #310030-119938 and #K-32K1-116460). Michael R Hamblin was supported by NIH grant R01AI050875, Center for Integration of Medicine and Innovative Technology (DAMD17-02-2-0006), CDMRP Program in TBI (W81XWH-09-1-0514) and Air Force Office of Scientific Research (FA9950-04-1-0079). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.