Deletion of p53-Related Protein Kinase Suppresses Solar UV-Induced Photocarcinogenesis by Inhibiting PD-L1 Expression and Enhancing CD8 T-Cell Infiltration

Sep 23, 2026

Uploaded by Franzy

Nonmelanoma skin cancers are primarily caused by solar UV exposure and represent the most common cancers in the United States. PRPK (p53-related protein kinase) is implicated in multiple cancers. In this study, epidermal-specific PRPK knockout mice were generated using CRISPR/Cas9 in SKH1 hairless mice with loxP-flanked PRPK alleles crossed with K14.Cre mice. Deletion significantly suppressed solar-simulated light–induced nonmelanoma skin cancer tumor growth and reduced cSCC cell growth via G1 arrest and apoptosis. Mechanistically, PRPK deletion inhibited PCNA and PD-L1 expression through downstream transcription factor pathways and increased CD8 T-cell infiltration while reducing IL-6, MIP-2, and VEGF, reprogramming the tumor microenvironment to support antitumor immunity.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages26

Reading Time1 h 6 min

AccessFree to download

Abstract

Introduction

Immunosuppressive tumor microenvironment and immune escape

Author Manuscr ipt Author Manuscr ipt Author Manuscr ipt Author Manuscript | | HHS Public Access
Author manuscript
J Invest Dermatol. Author manuscript; available in PMC 2025 December 19. | | --- | --- | Published in final edited form as: J Invest Dermatol. 2026 February ; 146(2): 405–417.e10. doi:10.1016/j.jid.2025.07.021 . Deletion of p53-Related Protein Kinase Suppresses Solar UV– Induced Photocarcinogenesis by Inhibiting PD-L1 Expression and Enhancing CD8 T-Cell Infiltration Qiushi Wang 1 , Eunmiri Roh 1,2 , Asad U. Khan 1 , Sally E. Dickinson3 , Georg T. Wondrak3 , Ann M. Bode 1 , Clara Curiel-Lewandrowski3,4 , Tianshun Zhang 1 1The Hormel Institute, University of Minnesota, Austin, Minnesota, USA 2 Department of Cosmetic Science, Kwangju Women’s University, Gwangju, Republic of Korea 3The University of Arizona Cancer Center, The University of Arizona, Tucson, Arizona, USA 4 Division of Dermatology, College of Medicine-Tucson, Tucson, Arizona, USA Abstract Nonmelanoma skin cancers are primarily caused by solar UV exposure and represent the most common cancers in the United States. PRPK (p53-related protein kinase) is a protein kinase that is involved in multiple cancers, including colon cancer, myeloma, and hepatocellular carcinoma. In this study, we generated epidermal-specific PRPK-knockout mice using CRISPR/ Cas9 technology in SKH1 hairless mice with loxP-flanked PRPK alleles, crossed with keratin 14-Cre (K14.Cre) mice. Our findings reveal that epidermal-specific deletion of PRPK significantly suppresses tumor growth in solar-simulated light–induced nonmelanoma skin cancer. Knocking down PRPK significantly suppresses cutaneous squamous cell carcinoma cell growth by inducing G1 phase arrest and promoting apoptosis. Mechanistically, PRPK deletion inhibits proliferating cell nuclear antigen and PD-L1 expression as well as the expression of transcription factors c-Myc, c-Jun, NF-κB, and activator protein-1, which mediate PD-L1 expression. Using a 3-dimensional culture system, we further demonstrate that PRPK deletion suppresses cutaneous squamous cell carcinoma cell growth. Flow cytometry analysis indicates that PRPK deletion enhances CD8 T-cell infiltration. This is accompanied by significant reductions in IL-6, MIP-2, and VEGF levels, reprogramming the tumor microenvironment to support CD8 T-cell infiltration. In summary, our This work is licensed under a Creative Commons Attribution 4.0 International License. To view a copy of this license, visit [https://](https://)[ ](https://)[creativecommons.org/licenses/by/4.0/](creativecommons.org/licenses/by/4.0/) Correspondence: Tianshun Zhang, The Hormel Institute University of Minnesota, 801 16th Avenue Northeast, Austin, Minnesota 55912, [USA. zhan4145@umn.edu](USA. zhan4145@umn.edu). AUTHOR CONTRIBUTIONS Conceptualization: QW, TZ; Data Curation: QW, TZ; Formal Analysis: QW, AK; Investigation: QW, ER, AK; TZ; Methodology: QW, ER, TZ; Resources: SD, GTW, CC-L, AMB, TZ; Supervision: TZ; Visualization: QW, TZ; Writing-Original Draft Preparation: QW, TZ; Writing-Review and Editing: SD, AMB, CC-L, TZ CONFLICT OF INTEREST The authors state no conflict of interest. ETHICS STATEMENT This study was conducted in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals from the National Institutes of Health. All animals were maintained in compliance with guidelines approved by the University of Minnesota Institutional Animal Care and Use Committee (protocol identification 2205–40061A), and all procedures involving animals were reviewed and approved by the Institutional Animal Care and Use Committee to ensure humane treatment and minimize suffering. Author Manuscr ipt Author Manuscr ipt Author Manuscr ipt Author Manuscript Wang et al. Page 2 study demonstrates that PRPK deletion suppresses solar UV–induced photocarcinogenesis by inhibiting PD-L1 expression and enhancing CD8 T-cell infiltration,

FAQs

How was epidermal-specific PRPK deletion achieved in the study?

Researchers generated epidermal-specific PRPK-knockout mice using CRISPR/Cas9 in SKH1 hairless mice with loxP-flanked PRPK alleles and crossed them with keratin 14-Cre (K14.Cre) mice.

What effects did PRPK deletion have on solar UV–induced nonmelanoma skin cancer?

PRPK deletion significantly suppressed tumor growth in solar-simulated light–induced nonmelanoma skin cancer.

Through what mechanisms did PRPK deletion suppress tumor growth and modulate immunity?

PRPK deletion promoted G1 phase arrest and apoptosis, inhibited PCNA and PD-L1 expression by suppressing transcription factor pathways (c-Myc, c-Jun, NF-κB, and AP-1), and enhanced CD8 T-cell infiltration while lowering IL-6, MIP-2, and VEGF levels.

Sep 23, 2026

Uploaded by Franzy