Targeting NOP14 remodels the tumor immune microenvironment and enhances the antitumor efficacy of PD-1 blockade in DLBCL.

Background: 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. Methods: 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-PCR, western blot, and immunohistochemistry (IHC). Stable NOP14-knockdown cell lines were established using lentiviral vectors to assess proliferation through EdU, colony formation, and CCK-8 assays Results: 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 Conclusion: Our findings establish NOP14 as a crucial oncogene and a key mediator of immune evasion in DLBCL that operates through the Wnt/β-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.