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:Beyond single biomarkers: multi-omics strategies to predict immunotherapy outcomes in blood cancers.
Beyond single biomarkers: multi-omics strategies to predict immunotherapy outcomes in blood cancers.
这些进步有望将免疫疗法从经验医学转变为精准医学,优化白血病、淋巴瘤和骨髓瘤患者的治疗结果。
免疫疗法彻底改变了血液癌症治疗,但由于原发性耐药、复发和危及生命的毒性,反应仍然不可预测。传统的生物标志物无法捕捉肿瘤-免疫相互作用的复杂性,因此需要综合方法。本综述探讨了多组学技术、基因组学、转录组学、蛋白质组学、代谢组学、空间组学和微生物组分析如何解码血液恶性肿瘤中免疫治疗疗效和不良事件的分子驱动因素。我们强调关键进展:基因组学揭示新抗原景观和 HLA 多样性塑造检查点抑制剂反应;转录组学鉴定预测 CAR-T 失败的 T 细胞耗竭特征;代谢组学揭示了 AML 中乳酸驱动的免疫抑制;空间组学绘制了与霍奇金淋巴瘤结果相关的免疫结构。监督机器学习算法(例如随机森林、支持向量机)集成这些层以构建细胞因子释放综合征 (CRS) 和耐药性的预测模型,而纵向 ctDNA 监测可实现动态治疗适应。基于 CRISPR 的表位编辑、计算机临床试验的数字孪生以及非编码 RNA 生物标志物等新兴前沿进一步完善了精准策略。尽管在数据集成、肿瘤可塑性和伦理框架方面面临挑战,多组学正在加速生物标志物驱动的试验设计(例如,组学分层的篮子试验)和以患者为中心的工具(用于实时代谢物跟踪的可穿戴传感器)。这篇综述的独特之处在于综合了这些快速的技术进步,不仅可以预测结果,还可以为其临床转化制定前瞻性路线图,为克服当前精准免疫肿瘤学的障碍提供独特的视角。总之,这些进步有望将免疫疗法从经验医学转变为精准医学,优化白血病、淋巴瘤和骨髓瘤患者的治疗结果。
Immunotherapy has revolutionized hematologic cancer treatment, yet responses remain unpredictable due to primary resistance, relapse, and life-threatening toxicities. Conventional biomarkers fail to capture the complexity of tumor-immune interactions, necessitating integrative approaches. This review explores how multi-omics technologies, genomics, transcriptomics, proteomics, metabolomics, spatial omics, and microbiome profiling, decode the molecular drivers of immunotherapy efficacy and adverse events in hematologic malignancies. We highlight key advances: genomics reveals neoantigen landscapes and HLA diversity shaping checkpoint inhibitor responses; transcriptomics identifies T-cell exhaustion signatures predictive of CAR-T failure; metabolomics uncovers lactate-driven immunosuppression in AML; and spatial omics maps immune architectures linked to Hodgkin lymphoma outcomes. Supervised machine learning algorithms (e.g., random forest, support vector machines) integrate these layers to build predictive models for cytokine release syndrome (CRS) and resistance, while longitudinal ctDNA monitoring enables dynamic therapy adaptation. Emerging frontiers like CRISPR-based epitope editing, digital twins for in silico clinical trials, and non-coding RNA biomarkers further refine precision strategies. Despite challenges in data integration, tumor plasticity, and ethical frameworks, multi-omics is accelerating biomarker-driven trial designs (e.g., basket trials with omics stratification) and patient-centric tools (wearable sensors for real-time metabolite tracking). This review distinguishes itself by synthesizing these rapid technological advances not only to predict outcomes but also to chart a forward-looking roadmap for their clinical translation, offering a unique perspective on overcoming the current barriers to precision immuno-oncology. Together, these advances promise to transform immunotherapy from empirical to precision medicine, optimizing outcomes for leukemia, lymphoma, and myeloma patients.
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