肿瘤细胞治疗研究
英文原题：The impact of the large B-cell lymphoma tumor microenvironment on efficacy of CD19-directed CAR-T immunotherapy.
The impact of the large B-cell lymphoma tumor microenvironment on efficacy of CD19-directed CAR-T immunotherapy.
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大 B 细胞淋巴瘤是一种侵袭性淋巴瘤亚型，在复发/难治性情况下预后较差。
大B细胞淋巴瘤是一种侵袭性淋巴瘤亚型，在复发/难治性情况下预后较差。尽管CD19 CAR-T 免疫疗法在长期生存方面取得了相当大的改善，但超过一半的患者未能实现持久缓解。更深入地理解肿瘤微环境中驱动治疗耐药的机制，对于指导开发能够克服免疫抑制因素的改良CAR-T 疗法至关重要。在这篇综述中，我们综合了当前关于大B细胞淋巴瘤微环境的组织学、细胞、分子和空间特征如何影响CD19 CAR-T 治疗后临床反应的知识，并指出了该领域的关键知识空白。我们讨论了旨在重编程免疫抑制性肿瘤微环境的新兴新型CAR-T 工程策略的临床试验数据，并强调了日益需要能够整合多模态、高维数据集的先进分析方法，以全面表征这一复杂的肿瘤生态系统。
Large B-cell lymphoma is an aggressive lymphoma subtype with poor outcomes in the relapsed and refractory setting. Despite considerable improvements in long-term survival with CD19 CAR-T immunotherapy, over half of patients do not achieve durable remissions. A deeper understanding of the mechanisms within the tumor microenvironment that drive treatment resistance is critical to informing the development of improved CAR-T therapies that can overcome immunosuppressive elements. In this review, we synthesize current knowledge on how histological, cellular, molecular and spatial features of the large B-cell lymphoma microenvironment influence clinical responses following CD19 CAR-T therapy and highlight key knowledge gaps in the field. We discuss data from clinical trials of emerging novel CAR-T engineering strategies aimed at reprogramming the immunosuppressive tumor microenvironment and underscore the growing need for advanced analytical approaches capable of integrating multimodal, high-dimensional datasets to comprehensively characterize this complex tumor ecosystem.
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