Discipline of Dermatology, Sydney Cancer Centre, The University of Sydney at Royal Prince Alfred Hospital, Camperdown, Sydney, NSW, Australia.
Br J Dermatol. 2010 Mar;162(3):637-41. doi: 10.1111/j.1365-2133.2009.09562.x. Epub 2009 Oct 26.
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.
This study aimed to determine the in vivo immune effects of PDT in humans.
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.
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%).
Topical PDT induced significant immune suppression, which could impair local antitumour immune responses and may thus contribute to treatment failure.
应用光敏剂后进行可见光照射（局部光动力疗法；PDT）越来越多地用于治疗非黑素瘤皮肤癌和光化性角化病前期。PDT 可以为手术提供一种美容效果更好的替代方法，但失败率为 10-40%。虽然一些鼠类研究表明 PDT 具有免疫增强作用，但其他研究报道了免疫抑制作用，这可能表明抗肿瘤免疫受损，从而导致肿瘤清除受损。
本研究旨在确定 PDT 在人体内的免疫效应。
使用 Mantoux 阳性的健康志愿者，我们用窄带红光（630nm；37J/cm²）照射背部的离散区域，同时或不预先应用 5-氨基酮戊酸（ALA）或甲基氨基酮戊酸（MAL）。相邻的未处理区域作为免疫完整的对照部位。然后在每个照射、未照射和对照部位中诱发结核菌素纯化蛋白衍生物（Mantoux 反应）的迟发型超敏反应，并使用红斑计和 Mantoux 直径测量来定量反应强度。通过比较治疗部位和对照部位的 Mantoux 强度，确定每种干预措施下每个志愿者的免疫抑制情况。
我们发现 MAL-PDT 和 ALA-PDT 均显著抑制了 Mantoux 红斑（分别为 30%和 50%）和直径（分别为 41%和 38%）。单独的红光显著抑制了直径（22%），但不抑制红斑（13%）。
局部 PDT 诱导了显著的免疫抑制，这可能会损害局部抗肿瘤免疫反应，并可能导致治疗失败。
