{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T08:18:43Z","timestamp":1793089123650,"version":"4.5.0"},"reference-count":43,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,11,26]],"date-time":"2024-11-26T00:00:00Z","timestamp":1732579200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>ETAA1 is recruited to DNA damage sites via its RPA -binding and ATR -activating domain (AAD) motifs, where RPA binding is crucial for ETAA1\u2019s regulation of ATR activity. <\/jats:p><\/jats:sec><jats:sec><jats:title>Methods &amp;amp; results<\/jats:title><jats:p>Our findings associate Programmed Death- Ligand1 (PD-L1) with the RPA1-ETAA1 axis, suggesting that upregulated RPA1 -dependent ETAA1 may facilitate PD-L1 nuclear accumulation. We observed strong correlations between ETAA1 and RPA1 with the components involved in HDAC2-mediated deacetylation, clathrin -dependent endocytosis, and PD-L1 nucleocytoplasmic shuttling, aligning with the established regulatory pathway of PD-L1 nuclear translocation. Moreover, nuclear PD-L1 transactivates a panel of pro-inflammatory and immune response transcription factors, potentially reshaping the tumor immune microenvironment. We identified a landscape of infiltrating lymphocytes influenced by ETAA1, finding that levels of ETAA1 were negatively correlated with CD8<jats:sup>+<\/jats:sup> T and Natural Killer T (NKT) cells, but positively correlated with CD4<jats:sup>+<\/jats:sup> T helper 2 (Th2) cells, cancer-associated fibroblasts (CAFs), myeloid-derived suppressor cells (MDSCs), neutrophils and regulatory T cells (Tregs), suggesting a potential role in immune evasion. Further analysis shows that the RPA1-ETAA1 axis is significantly associated with multiple metastasis mediators and unfavorable liver cancer progression, with higher expression observed in advanced stages and poorly differentiated subgroups. <\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion &amp;amp; conclusion<\/jats:title><jats:p>These findings expand the role of the RPA1-ETAA1 axis beyond DNA repair, highlighting its potential as a target for cancer therapy.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2024.1492531","type":"journal-article","created":{"date-parts":[[2024,11,26]],"date-time":"2024-11-26T06:26:49Z","timestamp":1732602409000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Exploring RPA1-ETAA1 axis via high-throughput data analysis: implications for PD-L1 nuclear translocation and tumor-immune dynamics in liver 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