{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T06:06:21Z","timestamp":1784700381828,"version":"3.55.0"},"reference-count":48,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T00:00:00Z","timestamp":1784678400000},"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>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Nucleolar Protein 14 (NOP14), a highly conserved factor in eukaryotes, is essential for pre-18S rRNA processing and small ribosomal subunit assembly. Emerging evidence underscores its pivotal regulatory role in the progression of various malignancies. Nevertheless, its functional involvement in Diffuse large B-cell lymphoma (DLBCL), particularly its capacity to modulate the tumor immune microenvironment, remains to be fully elucidated.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Genomic and clinical data from DLBCL patients were retrieved from the GEO database (GSE12195, GSE32018, GSE181063 and GSE10846) for integrated bioinformatics analysis. NOP14 expression was quantified via qRT\u2212PCR, western blot, and immunohistochemistry (IHC). Stable NOP14-knockdown cell lines were established using lentiviral vectors to assess proliferation through EdU, colony formation, and CCK\u22128 assays\n                      <jats:italic>in vitro<\/jats:italic>\n                      , as well as in the A20 syngeneic mouse model of DLBCL\n                      <jats:italic>in vivo<\/jats:italic>\n                      . To explore the underlying mechanism of NOP14, RNA sequencing was performed followed by KEGG enrichment analysis. Furthermore, flow cytometry was utilized to determine the correlation between NOP14 expression and the infiltration of immune cells. Finally, we developed cRGD-modified lipid nanoparticles encapsulating NOP14-siRNA (NOP14-siRNA@LNP) to assess its synergistic potential with anti-PD-1 therapy.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      NOP14 was significantly overexpressed in DLBCL tissues and cell lines, with elevated levels correlating with shorter overall survival and unfavorable clinicopathological features. Our findings reveal that NOP14 exerts a prominent dual role in driving tumor proliferation and facilitating immune evasion in DLBCL. Characterized as a cell-intrinsic oncogene, NOP14 directly sustains tumor growth, whereas its depletion significantly compromises DLBCL cell proliferation both\n                      <jats:italic>in vitro<\/jats:italic>\n                      and\n                      <jats:italic>in vivo<\/jats:italic>\n                      . Concurrently, NOP14 functions as an extrinsic regulator of the tumor microenvironment by impairing CD8\n                      <jats:sup>+<\/jats:sup>\n                      T cell infiltration and cytotoxic function to mediate immune escape. Mechanistically, NOP14 ablation inactivates the Wnt\/\u03b2-catenin\/c-Myc signaling cascade, which subsequently downregulates PD-L1 expression. This molecular shift successfully reverses the immunosuppressive state, markedly boosting tumor-infiltrating CD8\n                      <jats:sup>+<\/jats:sup>\n                      T cells and stimulating their IFN-\u03b3 production. Notably, the specific depletion of CD8\n                      <jats:sup>+<\/jats:sup>\n                      T cells significantly attenuated the effect of NOP14 on tumor growth. Additionally, cRGD-modified NOP14-siRNA@LNP successfully targets DLBCL via \u03b1v\u03b23 integrin recognition with excellent biocompatibility. NOP14-siRNA@LNP monotherapy effectively restricts tumor progression, and its combination with anti-PD-1 blockade exhibits strong synergy, maximizing CD8\n                      <jats:sup>+<\/jats:sup>\n                      T cell infiltration and activation by simultaneously neutralizing the function of NOP14.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Our findings establish NOP14 as a crucial oncogene and a key mediator of immune evasion in DLBCL that operates through the Wnt\/\u03b2-catenin\/c-Myc axis. Targeted NOP14 via NOP14-siRNA@LNP not only inhibits tumor growth but also sensitizes DLBCL to immune checkpoint blockade, offering a promising strategic framework for precision immunotherapy.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1799719","type":"journal-article","created":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T05:52:21Z","timestamp":1784699541000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Targeting NOP14 remodels the tumor immune microenvironment and enhances the antitumor efficacy of PD-1 blockade in DLBCL"],"prefix":"10.3389","volume":"17","author":[{"given":"Lu","family":"Zou","sequence":"first","affiliation":[{"name":"Department of Pharmacy, Qilu Hospital of Shandong University","place":["Jinan, Shandong, China"]},{"name":"School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University","place":["Jinan, Shandong, 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