Topical photodynamic therapy is immunosuppressive in humans.
BACKGROUND
Visible light irradiation after application of a photosensitizer (topical photodynamic therapy; PDT) is increasingly used to treat nonmelanoma skin cancers and premalignant actinic keratoses. PDT can provide a cosmetically superior alternative to surgery, but carries failure rates of 10-40%. While some murine studies have suggested immune enhancement by PDT, others reported immunosuppressive effects, which may indicate impaired antitumour immunity and thus compromised tumour clearance.


OBJECTIVE
This study aimed to determine the in vivo immune effects of PDT in humans.


METHODS
Using healthy, Mantoux-positive volunteers, we irradiated discrete areas of the back with narrowband red light (630 nm; 37 J cm(-2)), with and without prior application of 5-aminolaevulinic acid (ALA) or methyl aminolaevulinate (MAL). Adjacent, untreated areas served as immunologically intact control sites. Delayed-type hypersensitivity responses to tuberculin purified protein derivative (Mantoux reactions) were then elicited in each of the irradiated, unirradiated and control sites, and the intensity of the reactions was quantitated with an erythema meter and by measurement of Mantoux diameter. By comparing Mantoux intensity at treated and control sites, immunosuppression was determined in each volunteer for each intervention.


RESULTS
We found that both MAL-PDT and ALA-PDT significantly suppressed Mantoux erythema (by 30% and 50%, respectively) and diameter (41% and 38%). Red light alone significantly suppressed diameter (22%) but not erythema (13%).


CONCLUSIONS
Topical PDT induced significant immune suppression, which could impair local antitumour immune responses and may thus contribute to treatment failure.
Discipline of Dermatology, Sydney Cancer Centre, The University of Sydney at Royal Prince Alfred Hospital, Camperdown, Sydney, NSW, Australia.
Y J
YJ
Matthews
D L
DL
Damian
D000287:Administration, Topical; D000328:Adult; D000622:Aminolevulinic Acid / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D006968:Hypersensitivity, Delayed / Q000139:chemically induced; D007108:Immune Tolerance / Q000187:drug effects* / Q000276:immunology; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D008027:Light; D008297:Male; D008875:Middle Aged; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000627:therapeutic use*; D012867:Skin / Q000528:radiation effects; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000276:immunology; D016896:Treatment Outcome; D014374:Tuberculin Test; D055815:Young Adult
D007166:Immunosuppressive Agents; D017319:Photosensitizing Agents; D000622:Aminolevulinic Acid