Photodynamic therapy and anti-tumour immunity

Abstract

Photodynamic therapy (PDT) uses non-toxic photosensitizers and harmless visible light in combination with oxygen to produce cytotoxic reactive oxygen species that kill malignant cells by apoptosis and/or necrosis, shut down the tumour microvasculature and stimulate the host immune system. In contrast to surgery, radiotherapy and chemotherapy that are mostly immunosuppressive, PDT causes acute inflammation, expression of heat-shock proteins, invasion and infiltration of the tumour by leukocytes, and might increase the presentation of tumour-derived antigens to T cells.The principle of photodynamic therapy (PDT) was first proposed over 100 years ago 1 . A recent review in Nature Reviews Cancer by Rakesh Jain and colleagues described some of the historical milestones in the development of PDT as a cancer treatment2. Many of the photosensitizers (PSs) that have been studied since PDT was first proposed are based on a porphyrin-like nucleus 3 . PSs function as catalysts when they absorb visible light and then convert molecular oxygen to a range of highly reactive oxygen species (ROS). The ROS that are produced during PDT have been shown to destroy tumours by multifactorial mechanisms4 , 5 (FIG. 1). PDT has a direct affect on cancer cells, producing cell death by necrosis and/or apoptosis 6 . PDT also has an affect on the tumour vasculature, whereby illumination and ROS production causes the shutdown of vessels and subsequently deprives the tumour of oxygen and nutrients 7,8 . Finally, PDT also has a significant effect on the immune system 9-11 , which can be either immunostimulatory or immunosuppressive.Most of the commonly used cancer therapies are immunosuppressive. Chemotherapy and ionizing radiation delivered at doses sufficient to destroy tumours are known to be toxic to the bone marrow, which is the source of all cells of the immune system, and neutropaenia and other forms of myelosuppression are often the dose-limiting toxicity of these therapies. However, it should be noted that low doses of either ionizing radiation12 , 13 or chemotherapy14 can have immunostimulatory effects, including the induction of heat-shock © 2006 Nature Publishing Group Correspondence to M.R.H. Hamblin@helix.mgh.harvard.edu. Competing interests statementThe authors declare no competing financial interests. DATABASES NIH Public Access Author ManuscriptNat Rev Cancer. Author manuscript; available in PMC 2010 September 6. Published in final edited form as:Nat Rev Cancer. 2006 July ; 6(7): 535-545. doi:10.1038/nrc1894. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript proteins 15 . Less well known is the fact that major surgery can also have an immunosuppressive effect that leads to a significant diminution of lymphocyte and natural killer (NK) cell function 16 . The ideal cancer therapy would not only destroy the primary tumour, but at the same time trigger the immune system to recognize, track down and destroy any remaining tumour cells, be they at or near the site of the primary tumour or distant microm...

Is surgical debridement necessary in the diabetic foot treated with photodynamic therapy?

“…The action mechanism of PDT is based on the photo-activation of specific compounds, called photosensitizers, which trigger cell death and modulate the immune response [10,11]. As an anti-microbial therapy, PDT stands as a procedure that does not induce microbial resistance [11].…”

Molecular effectors and modulators of hypericin-mediated cell death in bladder cancer cells

“…Photodynamic therapy (PDT) utilizes a tumor-localizing photosensitizer and visible light to produce reactive oxygen species (ROS) (Dolmans et al, 2003). PDT efficacy relies on a combination of direct ROS-mediated cytotoxic effects, vascular damage and induction of inflammatory responses (Dolmans et al, 2003;Castano et al, 2006), indicating a critical role for the molecular interplay between cancer cells and the surrounding tumor environment in therapeutic outcome.…”

Potentiation of photodynamic therapy of cancer by complement: the effect of γ-inulin

“…In addition to further development of more potent photosensitising drugs and their selective tumour localization, a promising approach appears in exploiting the PDT-associated host response. Tumour PDT elicits a strong host response orchestrated by the innate immune system that culminates in the development of adaptive immunity against the treated lesion, and renders an important contribution to the therapy outcome (Henderson and Gollnick, 2003;Castano et al, 2006;Korbelik, 2006). It has recently become evident that complement system is engaged at multiple levels in the execution of this host response, including (i) initial recognition of endogenous danger signals generated by tumour-localised insult inflicted by PDT, (ii) incitement and propagation of the elicited inflammatory response, (iii) efferocytosis (dead cell removal), and (iv) tumour antigen presentation and promotion of adaptive immune response recognising the PDT-treated tumour as its target Korbelik and Sun, 2006).…”