Immune consequences induced by photodynamic therapy in non-melanoma skin cancers: a review

Photodynamic therapy (PDT) is widely used in dermatology to treat precancerous skin lesions and superficial non-melanoma skin cancers (NMSCs), including premalignant actinic keratosis, cutaneous squamous cell carcinoma in situ, and superficial basal cell carcinoma. The long-term cure rates of PDT range from 70 to 90% in NMSC patients, with excellent cosmetic results and good tolerance. However, the mechanism of action of PDT on tumors is complex. PDT not only kills tumor cells directly but also rapidly recruits immune cells to release inflammatory mediators to activate antitumor immunity. PDT-induced tumor death, also called immunogenic cell death, can trigger both innate and adaptive immune response, further enhancing the antitumor effect. For instance, inoculation of tumor cells killed via PDT to animals triggered a stronger antitumor immunity in vivo than tumor cell lysates produced by other treatments. More importantly, many immunotherapy regimens based on the immune effect of PDT have been developed and demonstrated to be a promising therapeutic method for cancer in pre-clinical trials. Therefore, increasing efforts have been undertaken to investigate the immune responses associated with PDT. In the present review, we first introduce the antitumor effect and the associated mechanisms of PDT in cancers. Then, we summarize studies on the immune responses induced by PDT in NMSCs. We also discuss the potential mechanisms underlying the process.