Photodynamic immunosuppression reduced by lowering rate of light delivery
MedWire News: Reducing the irradiation rate during photodynamic therapy (PDT) for non-melanoma skin cancer can prevent immunosuppression, say researchers.
PDT for skin cancer, consisting of topical photosensitizer application followed by irradiation with visible light in the presence of oxygen, has been shown to induce severe immunosuppression in patients, which can compromise immune-mediated clearance of tumors.
Slower irradiation has been shown to prevent immunosuppression in mice with skin cancer, possibly without compromising treatment efficacy, Diona Damian (Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia) and colleagues assessed whether this might also be the case in 15 healthy human volunteers with Fitzpatrick's skin type II and III who were Mantoux positive.
The team applied the photosensitizers 5-aminolevulinic acid and/or methyl aminolevulinate to a small selected area on the backs of the volunteers before irradiation with narrowband red light (632 nm) at a variety of doses and fluence rates. The Mantoux delayed-type hypersensitivity reaction was used to test for immunosuppression.
Damian and team observed that the red light irradiation caused significant and dose-responsive immunosuppression at the high fluence rate of 75 mWcm-2 currently used in clinical practice. However, this was not the case at a lower fluence rate of 15 or 45 mWcm-2.
In addition, the researchers found that PDT-induced oxidative DNA photolesions occurred when PDT was delivered at a high fluence rate, but not when it was delivered more slowly. These lesions are thought to be a trigger for immunosuppression.
"Topical PDT at high but not low-fluence rates causes both immunosuppression and induction of oxidative DNA photolesions in human skin," write the authors in the Journal of Investigative Dermatology.
"As both immunosuppression and DNA damage are recognized tumor promoters, this suggests that simply irradiating more slowly may have the potential to reduce tumor recurrence and boost cure rates," they conclude.
"Further studies are now urgently needed to assess the role of PDT immunosuppression in PDT treatment failures and the mechanisms of cell toxicity following low fluence-rate PDT."
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By Helen Albert