Synergistic Enhancement of PD-L1 Expression from DNA Repair Dysfunction and UV Exposure in Xeroderma Pigmentosum: Potential Therapeutic Role of PD-L1 Inhibitors

Yu‐Chen Lin

doi:10.1016/j.jdermsci.2026.04.008

Synergistic Enhancement of PD-L1 Expression from DNA Repair Dysfunction and UV Exposure in Xeroderma Pigmentosum: Potential Therapeutic Role of PD-L1 Inhibitors

2026-04-28

0

PRE

AI

Y

Yu‐Chen Lin

T

Tzu‐Yu Lin

Y

Yung-Chieh Chang

H

Hui‐Ching Cheng

Y

Yi-Kai Hong

W

Wilson Jr F. Aala

H

Haider H. Reyes

P

Ping‐Chen Hou

H

Hsin-Yu Huang

B

Bryan Edgar K. Guevara

C

Chun Hei Antonio Cheung

J

John A. McGrath

C

Chao‐Kai Hsu *

DOI：10.1016/j.jdermsci.2026.04.008

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Abstract

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• Homozygous XPA splicing mutation identified in a child with xeroderma pigmentosum • XP-associated skin carcinoma showed strong PD-L1 expression and pathway activation • XPA knockdown and UVC synergistically increase DNA damage and PD-L1 in keratinocytes • Co-culture assays revealed enhanced keratinocyte–T cell interaction under high PD-L1 • Findings support PD-1/PD-L1 blockade as a potential approach for XP skin cancers

Keywords:

XPA mutation

PD-L1 expression

DNA repair dysfunction

UV exposure

xeroderma pigmentosum

Synergistic Enhancement of PD-L1 Expression from DNA Repair Dysfunction and UV Exposure in Xeroderma Pigmentosum: Potential Therapeutic Role of PD-L1 Inhibitors

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