Back to Search
Start Over
Photodynamic Therapy–Induced Immunosuppression in Humans Is Prevented by Reducing the Rate of Light Delivery
- Source :
- Journal of Investigative Dermatology. 131:962-968
- Publication Year :
- 2011
- Publisher :
- Elsevier BV, 2011.
-
Abstract
- Photodynamic therapy (PDT) of non-melanoma skin cancers currently carries failure rates of 10-40%. The optimal irradiation protocol is as yet unclear. Previous studies showed profound immunosuppression after PDT, which may compromise immune-mediated clearance of these antigenic tumors. Slower irradiation prevents immunosuppression in mice, and may be at least as effective as high-fluence-rate PDT in preliminary clinical trials. The photosensitizers 5-aminolaevulinic acid and/or methyl aminolaevulinate were applied to discrete areas on the backs of healthy Mantoux-positive volunteers, followed by narrowband red light irradiation (632 nm) at varied doses and fluence rates. Delayed type hypersensitivity (Mantoux) reactions were elicited at test sites and control sites to determine immunosuppression. Human ex vivo skin received low- and high-fluence-rate PDT and was stained for oxidative DNA photolesions. PDT caused significant, dose-responsive immunosuppression at high (75 mW cm(-2)) but not low (15 or 45 mW cm(-2)) fluence rates. DNA photolesions, which may be a trigger for immunosuppression, were observed after high-fluence-rate PDT but not when light was delivered more slowly. This study demonstrates that the current clinical PDT protocol (75 mW cm(-2)) is highly immunosuppressive. Simply reducing the rate of irradiation, while maintaining the same light dose, prevented immunosuppression and genetic damage and may have the potential to improve skin cancer outcomes.
- Subjects :
- Adult
Male
Skin Neoplasms
Light
medicine.medical_treatment
Photodynamic therapy
Dermatology
Light delivery
Biochemistry
Young Adult
Methyl aminolaevulinate
medicine
Humans
Molecular Biology
Aged
Skin
Immunosuppression Therapy
Photosensitizing Agents
business.industry
Dose-Response Relationship, Radiation
Immunosuppression
Aminolevulinic Acid
Cell Biology
Middle Aged
medicine.disease
Light dose
Clinical trial
Photochemotherapy
Immunology
Cancer research
Drug Therapy, Combination
Female
Skin cancer
business
Ex vivo
Subjects
Details
- ISSN :
- 0022202X
- Volume :
- 131
- Database :
- OpenAIRE
- Journal :
- Journal of Investigative Dermatology
- Accession number :
- edsair.doi.dedup.....3632c3cf39dffe3161fad95419cfca2a