Therapeutic and immune effects of 5‐aminolevulinic acid photodynamic therapy on UVB‐induced squamous cell carcinomas in hairless mice

The therapeutic effects of 5‐aminolevulinic acid (ALA)‐mediated photodynamic therapy (PDT) on cutaneous squamous cell carcinoma (SCC) are not fully understood, and the usefulness of topical PDT in the treatment of SCC is still debatable. The most interesting aspect in SCC PDT is perhaps its potential in inducing antitumor immune responses. In this study, cutaneous SCCs were established by UVB irradiation of hairless mice and treated with multiple ALA PDT. Immunohistochemistry assays showed that ALA PDT could induce quick apoptosis, overexpression of TNFα and marked increases in DCs, CD4+ and CD8+ cells in tumor interstitium and subcutaneous connective tissues. However, a complete response was only achieved for small SCCs. The clinical value of ALA PDT‐induced specific antitumor immune responses in long‐term control of SCCs deserves further study.

[1]  R. Bissonnette,et al.  Multiple Large-Surface Photodynamic Therapy Sessions with Topical or Systemic Aminolevulinic Acid and Blue Light in UV-Exposed Hairless Mice , 2004, Journal of cutaneous medicine and surgery.

[2]  H. S. de Bruijn,et al.  Kinetics and localisation of PpIX fluorescence after topical and systemic ALA application, observed in skin and skin tumours of UVB-treated mice. , 1996, British Journal of Cancer.

[3]  Mladen Korbelik,et al.  PDT‐associated host response and its role in the therapy outcome , 2006, Lasers in surgery and medicine.

[4]  C. Sibata,et al.  A clinical review of PDT for cutaneous malignancies. , 2006, Photodiagnosis and photodynamic therapy.

[5]  C. Elmets,et al.  PHOTODYNAMIC THERAPY OF CHEMICALLY‐ AND ULTRAVIOLET B RADIATION‐INDUCED MURINE SKIN PAPILLOMAS BY CHLOROALUMINUM PHTHALOCYANINE TETRASULFONATE , 1992, Photochemistry and photobiology.

[6]  W. Xu,et al.  Evaluation of photodynamic therapy of skin cancers with δ-aminolevulinic acid , 2002 .

[7]  A. Boonstra,et al.  UVB irradiation modulates systemic immune responses by affecting cytokine production of antigen-presenting cells. , 2000, International immunology.

[8]  P. Cappugi,et al.  Squamous Cell Carcinoma of the Eyelid Treated with Photodynamic Therapy , 2004, Journal of chemotherapy.

[9]  Peter K. Lee,et al.  Reduction in the Incidence of Squamous Cell Carcinoma in Solid Organ Transplant Recipients Treated with Cyclic Photodynamic Therapy , 2010, Dermatologic surgery : official publication for American Society for Dermatologic Surgery [et al.].

[10]  G. Parrinello,et al.  Methylaminolaevulinate‐based photodynamic therapy of Bowen’s disease and squamous cell carcinoma , 2008, The British journal of dermatology.

[11]  J Moan,et al.  Fluorescence spectroscopy of normal mouse skin exposed to 5-aminolaevulinic acid and red light. , 2001, Journal of photochemistry and photobiology. B, Biology.

[12]  Barbara Owczarczak,et al.  Photodynamic therapy and anti‐tumor immunity , 2006, Lasers in surgery and medicine.

[13]  B. Hirshowitz,et al.  Modified Topical Photodynamic Therapy of Superficial Skin Tumors, Utilizing Aminolevulinic Acid, Penetration Enhancers, Red Light, and Hypertherntia , 1998, Dermatologic surgery : official publication for American Society for Dermatologic Surgery [et al.].

[14]  H. Wulf,et al.  Photodynamic therapy with topical methyl‐ and hexylaminolevulinate for prophylaxis and treatment of UV‐induced SCC in hairless mice , 2010, Experimental dermatology.

[15]  Zheng Huang,et al.  Combination of photodynamic therapy and immunomodulation for skin diseases—update of clinical aspects , 2011, Photochemical & photobiological sciences : Official journal of the European Photochemistry Association and the European Society for Photobiology.

[16]  Ryan W. Hick,et al.  From keratinocyte to cancer: the pathogenesis and modeling of cutaneous squamous cell carcinoma. , 2012, The Journal of clinical investigation.

[17]  S. Ibbotson.  An overview of topical photodynamic therapy in dermatology. , 2010, Photodiagnosis and photodynamic therapy.