Laser immunotherapy for cutaneous squamous cell carcinoma with optimal thermal effects to enhance tumour immunogenicity

Int J Hyperthermia. 2018 Dec;34(8):1337-1350. doi: 10.1080/02656736.2018.1446221. Epub 2018 Apr 16.

Abstract

Background: Laser immunotherapy is a new anti-cancer therapy combining photothermal therapy and immunostimulation. It can eliminate the tumours by damaging tumour cells directly and promoting the release of damage-associated molecular patterns (DAMPs) to enhance tumour immunogenicity. The aim of this study was to investigate the thermal effects of laser immunotherapy and to evaluate the effectiveness and safety of laser immunotherapy for cutaneous squamous cell carcinoma (cSCC).

Methods: The cell viability and the DAMPs productions of heat-treated cSCC A431 cells in different temperatures were investigated. Laser immunotherapy with the optimal thermal effect for DAMPs production was performed on SKH-1 mice bearing ultraviolet-induced cSCC and a patient suffering from a large refractory cSCC.

Results: The temperature in the range of 45-50 °C killing half of A431 cells had an optimal thermal effect for the productions of DAMPs. The thermal effect could be further enhanced by local application of imiquimod, an immunoadjuvant. Laser immunotherapy eliminated most tumours and improved the survival rate of the ultraviolet-induced cSCC-bearing SKH-1 mice (p < 0.05). The patient with cSCC treated by laser immunotherapy experienced a significant tumour reduction after laser immunotherapy increased the amounts of infiltrating lymphocytes in the tumour. No obviously adverse effect was observed in the mice experiment or in the clinical application.

Conclusions: Our results strongly indicate that laser immunotherapy with optimal thermal effects is an effective and safe treatment modality for cSCC.

Keywords: Cutaneous squamous cell carcinoma (cSCC); damage-associated molecular patterns (DAMPs); imiquimod; laser immunotherapy; photothermal.

Publication types

  • Case Reports
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic / therapeutic use*
  • Animals
  • Carcinoma, Squamous Cell / metabolism
  • Carcinoma, Squamous Cell / therapy*
  • Cell Line, Tumor
  • Combined Modality Therapy
  • Female
  • HMGB1 Protein / metabolism
  • HSP70 Heat-Shock Proteins / metabolism
  • HSP90 Heat-Shock Proteins / metabolism
  • Humans
  • Imiquimod / therapeutic use*
  • Immunotherapy*
  • Laser Therapy*
  • Mice
  • Middle Aged
  • Phototherapy*
  • Skin Neoplasms / metabolism
  • Skin Neoplasms / therapy*

Substances

  • Adjuvants, Immunologic
  • HMGB1 Protein
  • HSP70 Heat-Shock Proteins
  • HSP90 Heat-Shock Proteins
  • Imiquimod