Increased PD-L1 Expression in Human Skin Acutely and Chronically Exposed to UV Irradiation.
Journal
Photochemistry and photobiology
ISSN: 1751-1097
Titre abrégé: Photochem Photobiol
Pays: United States
ID NLM: 0376425
Informations de publication
Date de publication:
07 2021
07 2021
Historique:
received:
11
01
2021
accepted:
18
02
2021
pubmed:
23
2
2021
medline:
15
2
2022
entrez:
22
2
2021
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 33615483
doi: 10.1111/php.13406
pmc: PMC8277687
mid: NIHMS1678447
doi:
Substances chimiques
B7-H1 Antigen
0
CD274 protein, human
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
778-784Subventions
Organisme : NCI NIH HHS
ID : P01 CA229112
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA023074
Pays : United States
Informations de copyright
© 2021 American Society for Photobiology.
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