Increased PD-L1 Expression in Human Skin Acutely and Chronically Exposed to UV Irradiation

Sally E. Dickinson, Maria Khawam, Viktoria Kirschnerova, Prajakta Vaishampayan, Sara M. Centuori, Kathylynn Saboda, Valerie S. Calvert, Emanuel F. Petricoin, Clara Curiel-Lewandrowski

Research output: Contribution to journalArticlepeer-review

Abstract

Overexpression of PD-L1 (CD274) on tumor cells may represent a hallmark of immune evasion, and overexpression has been documented in several tumors including cutaneous squamous cell carcinoma (cSCC). While PD-L1/PD-1 activity in the skin has been primarily described in inflammatory models, our goal was to examine PD-L1 expression in human keratinocytes exposed to UV irradiation. We assessed PD-L1 expression in human sun-protected (SP) and sun-damaged (SD) skin, actinic keratosis (AK), and cSCC using IHC and protein microarray. Both methods found low baseline levels of PD-L1 in SP and SD skin and significantly increased expression in cSCC. Next, we examined PD-L1 expression in acute models of UV exposure. In human SP skin exposed to 2-3 MED of UV (n = 20), epidermal PD-L1 was induced in 70% of subjects after 24 h (P = 0.0001). SKH-1 mice exposed to acute UV also showed significant epidermal PD-L1 induction at 16, 24 and 48 h. A time- and dose-dependent induction of PD-L1 was confirmed in cultured human keratinocytes after UV, which was markedly reduced in the presence of MEK/ERK, JNK or STAT3 inhibitors. These findings suggest that UV induces upregulation of PD-L1 through established, pharmacologically targetable stress-signaling pathways in keratinocytes.

Original languageEnglish (US)
JournalPhotochemistry and Photobiology
DOIs
StateAccepted/In press - 2021

ASJC Scopus subject areas

  • Radiation
  • Biochemistry
  • Physical and Theoretical Chemistry

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