Abstract 2979: Deletion of p53-related protein kinase (TP53RK) suppresses solar UV-induced photocarcinogenesis by inhibiting PDL1 expression and enhancing CD8+ T cell infiltration

Abstract Nonmelanoma skin cancers (NMSCs), including cutaneous squamous cell carcinoma (cSCC), are primarily caused by solar ultraviolet (UV) exposure and represent the most common cancers in the United States. TP53RK (p53-related protein kinase, also known as PRPK) is a protein kinase involved in multiple cancer progression such as colon cancer, myeloma and skin cancer. In this study, we generated epidermal-specific TP53RK knockout mice using CRISPR/Cas9 technology in SKH1 hairless mice with loxP-flanked TP53RK alleles, crossed with keratin 14-Cre (K14.Cre) mice. Our findings reveal that epidermal-specific deletion of TP53RK significantly suppresses tumor growth in solar-simulated light (SSL)-induced NMSC. Mechanistically, TP53RK deletion inhibits proliferating cell nuclear antigen (PCNA) and programmed death-ligand 1 (PDL1) expression, as well as the transcription factors c-Myc, c-Jun, and NF-κB, which mediate PDL1 expression. Using a 3D culture system, we further demonstrate that TP53RK deletion suppresses cSCC cell growth. Flow cytometry analysis indicates that TP53RK deletion enhances CD8+ T cell infiltration into the tumor microenvironment. 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 study demonstrates that TP53RK deletion suppresses solar UV induced photocarcinogenesis by inhibiting PDL1 expression and enhancing CD8+ T cell infiltration, highlighting its potential as a therapeutic target for NMSC. Citation Format: Qiushi Wang, Eunmiri Roh, Asad Khan, Sally Dickinson, Georg T. Wondrak, Ann Bode, Clara Curiel-Lewandrowski, Tianshun Zhang. Deletion of p53-related protein kinase (TP53RK) suppresses solar UV-induced photocarcinogenesis by inhibiting PDL1 expression and enhancing CD8+ T cell infiltration [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 2979.