决定异体 CAR T 细胞排斥与扩增的细胞和分子机制
Cellular and molecular mechanisms determining allogeneic CAR T cell rejection and expansion.
我们评估了11例接受单一批次cemacabtagene ansegedleucel(cema-cel)治疗的大B细胞淋巴瘤患者,cemacabtagene ansegedleucel是一种异体抗CD19 CAR T产品。
英文原题:Identification of CD7 as a novel biomarker of embryonal hepatoblastoma.
Identification of CD7 as a novel biomarker of embryonal hepatoblastoma.
CD7在人HB中表达,尤其是在胚胎型组织学亚型中,并且似乎与肿瘤进展和不良临床结局相关。尽管如此,靶向CD7的CAR-T 细胞可作为胚胎型HB的一种有前景的免疫疗法。
本研究旨在探讨分化簇7(CD7)在肝母细胞瘤(HB)中的表达及其作为HB新型生物标志物的潜在应用价值。
通过bulk、单细胞RNA测序和空间转录组分析在基因水平上研究了人HB样本中CD7的表达,此外还通过免疫组化(IHC)染色在蛋白水平上进行了研究。还进行了基于CD7基因表达的生存分析,以及CD7-SECTM1受体-配体基因对的基因集富集分析(GSEA)。
CD7在人HB中于基因水平通过多种生物信息学分析及蛋白水平通过IHC均呈差异性表达,在胚胎型HB中表达水平显著更高。相反,CD7在其他原发性成人肝脏肿瘤中不表达。CD7高表达的HB病例5年无事件生存率更差(P = 0.016),GSEA显示CD7与胚胎型MYCN转录因子相关,也与促肿瘤激酶如JAK3相关,与MAPK14和MAPK3则呈边缘相关。
PURPOSE: This study aimed to investigate the expression of cluster of differentiation 7 (CD7) in hepatoblastoma (HB) and its potential use as a novel biomarker of HB. METHODS: CD7 expression was investigated in human HB samples at the gene level by bulk, single-cell RNA sequencing, and spatial transcriptomic analyses, in addition to the protein level by immunohistochemical (IHC) staining. CD7 gene expression-based survival analysis was also conducted, along with gene set enrichment analysis (GSEA) of the CD7-SECTM1 receptor-ligand gene pair. RESULTS: CD7 was differentially expressed in human HB at both the gene level by various bioinformatics analyses, and the protein level by IHC, with remarkably higher expression levels in embryonal HB. Conversely, CD7 was not expressed in other primary adult liver tumors. CD7 high HB cases showed poorer 5-year event-free survival (P = 0.016), and GSEA demonstrated that CD7 is linked to the embryonal MYCN transcription factor, as were protumor kinases such as JAK3, and marginally MAPK14 and MAPK3. CONCLUSION: CD7 is expressed in human HB, especially the embryonal histological subtype, and appears to be linked to tumor progression and poor clinical outcomes. Nevertheless, CD7-targeted chimeric antigen receptor T cells could be proposed as a promising immunotherapy for embryonal HB.
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