SNRPB drives pan-cancer tumorigenesis and immunotherapy resistance via immune microenvironment remodeling

Background: Small nuclear ribonucleoprotein polypeptide B (SNRPB) has been implicated in tumor progression, but its pan-cancer expression landscape, clinical significance, and therapeutic potential remain incompletely understood. This study aimed to comprehensively characterize SNRPB across multiple cancer types. Methods: We performed pan-cancer analysis of the SNRPB gene expression using data from 33 cancer types, including comparisons with normal tissues, subcellular localization assessment, and single-cell transcriptomic profiling. Survival outcomes were evaluated via Cox regression and Kaplan–Meier analyses. Immunotherapy relevance was assessed using Tumor Immune Dysfunction and Exclusion scores, immune checkpoint inhibitor response prediction in mouse models, and correlations with established immunotherapy biomarkers. Functional experiments included SNRPB knockdown in diverse cancer cell lines to measure proliferation and invasion, as well as in vivo studies in subcutaneous syngeneic models combining SNRPB depletion with anti–PD-1 therapy. Results: The SNRPB gene was upregulated in most cancer types compared with normal tissues and predominantly localized to the nucleus. Single-cell analysis revealed widespread expression, especially in tumor cells and macrophages/monocytes. High SNRPB expression strongly correlated with worse survival across multiple cancers, most notably in kidney renal clear cell carcinoma. Elevated SNRPB was associated with immunotherapy resistance, as indicated by higher Tumor Immune Dysfunction and Exclusion scores in many cancers, poorer predicted responses to immune checkpoint inhibitors in mouse models, and correlations with known immunotherapy biomarkers and immune regulators. SNRPB knockdown potently inhibited proliferation and invasion in various cancer cell lines and suppressed kidney renal clear cell carcinoma cell growth in vitro . In vivo , combining SNRPB depletion with anti–PD-1 therapy enhanced therapeutic efficacy in subcutaneous syngeneic models by increasing CD8 + T-cell infiltration. Conclusions: SNRPB serves as a prognostic biomarker, a driver of tumor progression, and a promising therapeutic target. Its broad upregulation, association with poor survival and immunotherapy resistance, and functional role in promoting malignancy support the potential of targeting SNRPB to improve cancer treatment, particularly in combination with immune checkpoint blockade.