Immunological effects of photodynamic therapy in the treatment of actinic keratosis and squamous cell carcinoma

Abstract

The use of photodynamic therapy is extensive, due to its antitumoral, antibacterial and photorejuvenation effects. It destroys tumor via direct cell destruction and indirectly via vascular shutdown, induction of acute local inflammatory response and activation of the immune system. Both innate and adaptive immune cells are involved in the immunological effects of photodynamic therapy. In addition to UV-induced DNA damage, inflammation and immunosuppression are also essential elements in the pathogenesis of actinic keratosis. Both immunosuppression induced by UV and defective immune response to dysplastic keratinocytes may be the target of photodynamic therapy to eliminate actinic keratosis. These elements are discussed in the present review, highlighting the possible mechanism of photodynamic therapy to effectively treat actinic keratosis.

DNA Strand Break Properties of Protoporphyrin IX by X-ray Irradiation against Melanoma

“…Moreover, RT may increase the antitumor response by promoting antigen presentation and T-cell activation [45]. 5-ALA PDT can activate an otherwise quiescent local immune response under certain circumstances [46][47][48][49]. PDT may induce vascular shutdown by destroying endothelial cells and the vascular basement membrane, resulting in oxygen deprivation.…”

“…PDT may induce vascular shutdown by destroying endothelial cells and the vascular basement membrane, resulting in oxygen deprivation. Moreover, acute local inflammatory and immunological reactions, involving the innate and adaptive immune system, are induced as an indirect effect of PDT [46]. For RDT with 5-ALA, ionized calcium-binding adapter molecule 1 (Iba1)-positive macrophages were observed at the surface and within the subcutaneous tumors after treatment with multidose ionizing irradiation in combination with 5-ALA as demonstrated by the red immunohistochemical staining observed in samples from a rat glioma subcutaneous model [10].…”

Immunological Consequences of Nanoparticle‐Mediated Antitumor Photoimmunotherapy

“…DAMPs include the calreticulin (CRT), adenosine triphosphate (ATP), high‐mobility group box 1 (HMGB1), heat shock proteins (HSPs) 70 and HSP90 . Among them, calreticulin is an endoplasmic reticulum‐resistant protein, which facilitates the phagocytosis of irradiated dead cancer cells by macrophages and DCs . ATP attracts the DCs into the tumor, and HMGB1 promotes the DC maturation by secreting pro‐inflammatory cytokines.…”

“…ATP attracts the DCs into the tumor, and HMGB1 promotes the DC maturation by secreting pro‐inflammatory cytokines. HSPs can stimulate the migration and maturation of DCs by upregulating the expression of costimulatory molecules (CD40, CD80, Cd83, and CD86) . Altogether, DAMPs enhanced the cross‐presentation of tumor‐derived antigens by DCs to stimulate both CD8 + T cells and CD4 + T cells, which are responsible for building an immunological memory against the specific tumor.…”

“…On the other hand, PTT relies on the ability of photothermal agents to convert light energy into heat to destroy cancer cells . In addition to direct killing, phototherapies are also well‐known to improve the immunogenicity of the tumor by releasing cellular death‐associated molecular patterns (CDAMPs) and damage‐associated molecular patterns (DAMPs) that can be recognized by the innate immunity alert elements . At the molecular level, the phototherapies induce nonrepairable DNA debris of cancer cells (tumor antigens), which are captured and presented by antigen presenting cells (APCs) in the tumor draining lymph nodes to T cells to stimulate antitumor immunity .…”