γδ T 细胞调节小细胞肺癌中的抗肿瘤免疫
γδ T cells modulate anti-tumor immunity in small cell lung cancer.
我们的发现表明,活化的γδ T细胞可能是SCLC治疗的有价值靶点。
英文原题:SNRPB2 facilitates esophageal squamous cell carcinoma oncogenesis and progression via E2F4 stabilization.
SNRPB2通过稳定E2F4和调控细胞周期基因促进ESCC进展。它还与ESCA中的免疫浸润和基因表达相关。SNRPB2可能作为食管癌的预后生物标志物和潜在治疗靶点。
食管癌(ESCA)是一种高度侵袭性的恶性肿瘤,预后较差。小核核糖核蛋白多肽B2(SNRPB2)是剪接体的核心组分,参与前体mRNA剪接。然而,其在肿瘤发生和进展中的作用仍 largely 不清楚。本研究旨在评估SNRPB2在ESCA中的临床相关性和预后价值。
使用GEPIA2和cBioPortal分析SNRPB2 mRNA表达和基因改变。通过免疫组织化学在石蜡包埋的食管鳞状细胞癌(ESCC)组织中评估蛋白表达。在ESCC细胞系中进行功能实验以确定SNRPB2的生物学作用。使用TIMER、TISIDB、TISCH、Gene Ontology(GO)和Gene Set Enrichment Analysis(GSEA)进行免疫相关和功能分析。使用放线菌酮(CHX)追踪实验评估蛋白稳定性。
SNRPB2 mRNA 在 ESCA 中表达上调,并与肿瘤进展和不良预后相关。免疫组化证实 ESCC 中 SNRPB2 蛋白高表达,与脉管癌栓、淋巴结转移、临床分期和肿瘤分级相关。敲低 SNRPB2 在体外和体内均显著抑制 ESCC 细胞增殖、迁移和侵袭。GSEA 表明 SNRPB2 抑制 Rb/E2F 通路。机制上,SNRPB2 通过阻止 E2F4 蛋白的蛋白酶体降解来稳定 E2F4 蛋白,而 E2F4 过表达逆转了沉默 SNRPB2 的抑瘤效应。免疫分析显示,SNRPB2 表达与活化 CD8 + T 细胞、γδ T 细胞、树突状细胞和单核细胞浸润增加相关,也与免疫相关基因包括 PDCD1、CD274、CTLA4、HLA-DRA 和 B2M 相关。这些发现提示 SNRPB2 在 ESCA 中具有促进肿瘤进展和调节免疫微环境的双重作用。
INTRODUCTION: Esophageal cancer (ESCA) is a highly aggressive malignancy with poor prognosis. Small nuclear ribonucleoprotein polypeptide B2 (SNRPB2) is a core component of the spliceosome involved in pre-mRNA splicing. However, its role in tumor development and progression remains largely unclear. This study aimed to evaluate the clinical relevance and prognostic value of SNRPB2 in ESCA. METHODS: SNRPB2 mRNA expression and genetic alterations were analyzed using GEPIA2 and cBioPortal. Protein expression was assessed by immunohistochemistry in paraffin-embedded esophageal squamous cell carcinoma (ESCC) tissues. Functional assays in ESCC cell lines were conducted to determine the biological role of SNRPB2. Immune-related and functional analyses were performed using TIMER, TISIDB, TISCH, Gene Ontology (GO), and Gene Set Enrichment Analysis (GSEA). Cycloheximide (CHX) chase assays were used to assess protein stability. RESULTS: SNRPB2 mRNA was upregulated in ESCA and associated with tumor progression and poor prognosis. Immunohistochemistry confirmed high SNRPB2 protein expression in ESCC, correlating with vessel carcinoma embolus, lymph node metastasis, clinical stage, and tumor grade. SNRPB2 knockdown significantly inhibited ESCC cell proliferation, migration, and invasion in vitro and in vivo . GSEA indicated that SNRPB2 suppresses the Rb/E2F pathway. Mechanistically, SNRPB2 stabilized E2F4 protein by preventing its proteasomal degradation, and E2F4 overexpression reversed the tumor-suppressive effects of SNRPB2 silencing. Immune analyses showed that SNRPB2 expression correlated with increased infiltration of activated CD8 + T cells, γδ T cells, dendritic cells, and monocytes, as well as immune-related genes including PDCD1 , CD274 , CTLA4 , HLA-DRA , and B2M . These findings suggest a dual role for SNRPB2 in promoting tumor progression and modulating the immune microenvironment in ESCA. CONCLUSION: SNRPB2 promotes ESCC progression by stabilizing E2F4 and regulating cell cycle genes. It is also associated with immune infiltration and gene expression in ESCA. SNRPB2 may serve as a prognostic biomarker and potential therapeutic target in esophageal cancer.
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