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:Personalized Immunotherapy for T Cell Lymphomas: From Immune Escape to Precision Therapeutics.
这些进展为PTCLs的治疗指明了一条从经验主义走向精准治疗的道路。
尽管淋巴瘤免疫治疗近期取得了进展,外周 T 细胞淋巴瘤(PTCL)患者的结局仍然很差。PTCL 的挑战反映了该疾病群体显著的生物学异质性和相对罕见性、其对常规化疗的耐药性,以及产生确定性临床证据的巨大困难。然而,对 PTCL 免疫基因组学和微环境基础的深入认识已揭示了多种免疫逃逸机制,涵盖抗原呈递、凋亡信号、黏附缺陷以及广泛的肿瘤微环境重塑。这些脆弱性为新型免疫治疗策略——检查点抑制剂、CAR-T 和 NK 细胞平台、双特异性抗体、溶瘤病毒和免疫调节剂——提供了坚实的理论基础。早期研究显示出令人鼓舞但不一致的活性,而应答的可变性凸显了迫切需要以生物标志物驱动的分层,以实现个性化方法和具有临床意义的疗效。本综述综合了当前关于 PTCL 免疫失调的文献,以及 PTCL 免疫治疗的进展,概述了支持这些方法的生物学依据。我们讨论了分子、转录组和微环境分析以及循环生物标志物的方法,这些方法可能使适应性试验设计和个性化治疗策略成为可能。总之,这些进展为 PTCL 开辟了一条从经验主义走向精准治疗的道路。
Despite recent progress in lymphoma immunotherapy, outcomes for patients with peripheral T cell lymphomas (PTCLs) remain poor. The challenge of PTCLs reflects the profound biological heterogeneity and relative rarity of this disease group and its resistance to conventional chemotherapy, as well as the formidable challenge of generating definitive clinical evidence. However, deepening insight into the immunogenomic and microenvironmental basis of PTCL has revealed diverse mechanisms of immune escape, spanning defects in antigen presentation, apoptotic signaling, adhesion, and extensive tumor microenvironmental remodeling. These vulnerabilities provide a sound rationale for novel immunotherapeutic strategies-checkpoint inhibitors, CAR-T and NK cell platforms, bispecific antibodies, oncolytic viruses, and immunomodulatory agents. Early studies show encouraging but inconsistent activity, and the variability in response highlights the urgent need for biomarker-driven stratification to deliver personalized approaches and clinically meaningful efficacy. This review synthesizes the current literature on the immune dysregulation of PTCLs, as well as advances in PTCL immunotherapy, outlining the biological rationale underpinning these approaches. We discuss approaches to molecular, transcriptomic, and microenvironmental profiling with circulating biomarkers that could enable adaptive trial designs and personalized treatment strategies. Together, these developments chart a path away from empiricism and toward precision therapy in PTCLs.
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