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:Long Non-Coding RNAs and Circular RNAs in the Pathobiology of T-Cell Lymphoma.
外周T细胞淋巴瘤(PTCLs)是一组异质性临床侵袭性成熟T细胞和自然杀伤(NK)细胞肿瘤,在西方国家约占所有非霍奇金淋巴瘤的10-15%。
外周T细胞淋巴瘤(PTCLs)是一组异质性、临床侵袭性强的成熟T细胞和自然杀伤(NK)细胞肿瘤,在西方国家约占所有非霍奇金淋巴瘤的10-15%。最常见的亚型包括结外NK/T细胞淋巴瘤(ENKTL)、淋巴结T滤泡辅助细胞淋巴瘤、外周T细胞淋巴瘤,非特指型(PTCL-NOS)、间变性大细胞淋巴瘤(ALK阳性和ALK阴性)以及T细胞淋巴母细胞淋巴瘤。非编码RNA(ncRNAs)构成人类转录组的大部分,在调控基因表达、细胞增殖、分化、迁移和凋亡中发挥关键作用。其中,长链非编码RNA(lncRNAs)和环状RNA(circRNAs)已成为PTCLs淋巴瘤发生和疾病进展的关键调控因子。这些分子通过染色质重塑、转录调控、竞争性内源RNA活性以及与RNA结合蛋白的相互作用,调节多种致癌通路,从而影响增殖、免疫逃逸、治疗耐药和临床结局。代表性例子包括lncRNA TCLlnc1,其通过激活转化生长因子-(TGF-)信号促进PTCL进展,以及circRNAs circKIF4A、circADARB1和circ-LAMP1,它们分别调控涉及PDK1/BCL11A、STAT3和DDR2的miRNA依赖性信号网络。在本综述中,我们总结了目前对lncRNAs和circRNAs在PTCL及相关T细胞和NK细胞肿瘤中的生物学和临床作用的理解,并强调它们作为诊断和预后生物标志物以及治疗靶点的潜力。我们还讨论了将基于ncRNA的方法整合到T细胞淋巴瘤精准医学中的最新进展和未来方向。
Peripheral T-cell lymphomas (PTCLs) are a heterogeneous group of clinically aggressive mature T-cell and natural killer (NK)-cell neoplasms that account for approximately 10-15% of all non-Hodgkin lymphomas in Western countries . The most common subtypes include extranodal NK/T-cell lymphoma (ENKTL), nodal T-follicular helper cell lymphomas, peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS), anaplastic large cell lymphoma (ALK-positive and ALK-negative), and T-cell lymphoblastic lymphoma. Non-coding RNAs (ncRNAs) constitute the majority of the human transcriptome and play critical roles in regulating gene expression, cellular proliferation, differentiation, migration, and apoptosis. Among these, long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs) have emerged as key regulators of lymphomagenesis and disease progression in PTCLs. These molecules modulate diverse oncogenic pathways through chromatin remodeling, transcriptional regulation, competing endogenous RNA activity, and interactions with RNA-binding proteins, thereby influencing proliferation, immune evasion, treatment resistance, and clinical outcomes. Representative examples include the lncRNA TCLlnc1, which promotes PTCL progression through activation of transforming growth factor- (TGF- ) signaling, and the circRNAs circKIF4A, circADARB1, and circ-LAMP1, which regulate miRNA-dependent signaling networks involving PDK1/BCL11A, STAT3, and DDR2, respectively. In this review, we summarize the current understanding of the biological and clinical roles of lncRNAs and circRNAs in PTCL and related T-cell and NK-cell neoplasms and highlight their potential as diagnostic and prognostic biomarkers as well as therapeutic targets. We also discuss recent advances and future directions for integrating ncRNA-based approaches into precision medicine for T-cell lymphoma.
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