CAR-T(CAR-T)细胞疗法在非肿瘤性疾病中的应用
Chimeric antigen receptor T (CAR-T) cell therapy in non-oncological diseases.
CAR-T(CAR-T)细胞在血液系统恶性肿瘤中的应用推动了这种免疫治疗形式的显著进展。
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Cytokine-mediated intrinsic and extrinsic regulation of anti-tumor adoptive T cell therapy.
Cytokine-mediated intrinsic and extrinsic regulation of anti-tumor adoptive T cell therapy.
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过继T细胞疗法改变了血液系统恶性肿瘤的治疗,但在实体瘤中难以实现疾病控制,主要障碍仍是T细胞功能障碍和免疫抑制性肿瘤微环境(TME)。细胞因子是调控T细胞命运和TME的重要因子,因此细胞因子工程是克服这些局限的关键手段。本文综述近期进展:一类内在策略将细胞因子支持直接整合进工程化T细胞产品,另一类外在策略则将细胞因子递送至肿瘤部位以重塑TME;并全面分析这些策略,以指导合理选择和联合应用。我们进一步重点介绍可诱导产生超越天然T细胞生物学边界的新型T细胞状态的合成细胞因子和受体设计。最后,我们提出“虚拟细胞因子网络”这一框架,用于预测任何设计的细胞因子干预所触发的患者特异性免疫级联反应,为个体化、细胞因子指导的过继T细胞治疗提供路径。
Adoptive T cell therapy has transformed the treatment of hematologic malignancies but fails to control solid tumors, where T cell dysfunction and an immunosuppressive tumor microenvironment (TME) remain the central barriers. Cytokines are essential regulators of both T cell fate and the TME, making cytokine engineering a key lever for overcoming these limitations.
Here we review recent advances in intrinsic strategies that embed cytokine support directly into the engineered T cell product and extrinsic strategies that deliver cytokines to the tumor site to remodel the TME, providing a comprehensive analysis to guide rational strategy selection and combination.
We further highlight synthetic cytokine and receptor designs that induce novel T cell states beyond the boundaries of natural T cell biology.
Finally, we propose virtual cytokine networks as a framework for predicting patient-specific immune cascades triggered by any designed cytokine intervention, providing a path toward personalized cytokine-guided adoptive T cell therapy.
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