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Solar Simulated Light Induces Cutaneous Squamous Cell Carcinoma in Inbred Mice: A Clinically Relevant Model to Investigate T-Cell Responses

      More than one million cutaneous squamous cell carcinomas (cSCCs) are diagnosed annually in the United States (
      • Rogers H.W.
      • Weinstock M.A.
      • Feldman S.R.
      • Coldiron B.M.
      Incidence estimate of nonmelanoma skin cancer (keratinocyte carcinomas) in the U.S. population 2012.
      ). The main causal factor of cSCC is UV exposure from sunlight, which is made of 95% UVA and 5% UVB at the Earth’s surface. UVA and UVB cause cyclobutane pyrimidine dimers in DNA and oxidative damage through the formation of ROS. The ratio of cyclobutane pyrimidine dimers to oxidative DNA damage products is ∼800 times greater in UVB than in UVA (
      • Zhang X.
      • Rosenstein B.S.
      • Wang Y.
      • Lebwohl M.
      • Mitchell D.M.
      • Wei H.
      Induction of 8-oxo-7,8-dihydro-2'-deoxyguanosine by ultraviolet radiation in calf thymus DNA and HeLa cells.
      ). In addition, UVA and UVB have distinct effects on keratinocyte signaling pathways, including apoptosis (
      • Bito T.
      • Sumita N.
      • Masaki T.
      • Shirakawa T.
      • Ueda M.
      • Yoshiki R.
      • et al.
      Ultraviolet light induces Stat3 activation in human keratinocytes and fibroblasts through reactive oxygen species and DNA damage.
      ;
      • Syed D.N.
      • Afaq F.
      • Mukhtar H.
      Differential activation of signaling pathways by UVA and UVB radiation in normal human epidermal keratinocytes.
      ). Thus, solar simulated light (SSL) is the most physiological method to generate a murine cSCC model recapitulating specific mutations and biological responses found in human disease.

      Abbreviations:

      cSCC (cutaneous squamous cell carcinoma), MHC (major histocompatibility complex), SSL (solar simulated light), TDLN (tumor-draining lymph node)
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