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.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Microfluidic perspectives on chimeric antigen receptor T-cell migration in solid tumours: highlighting physical confinement as a key barrier.
Microfluidic perspectives on chimeric antigen receptor T-cell migration in solid tumours: highlighting physical confinement as a key barrier.
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嵌合抗原受体(CAR)T细胞迁移并浸润实体瘤,仍是癌症免疫治疗面临的核心挑战。趋化因子梯度、细胞外基质(ECM)刚度和免疫抑制信号等因素已得到充分研究,而肿瘤结构造成的物理限域日益被认为是关键屏障。肿瘤相关ECM重塑会产生微米和纳米尺度的几何约束,显著改变免疫细胞(尤其CAR-T 细胞)在肿瘤微环境(TME)中的迁移方式。本文主张,应将物理限域置于细胞迁移障碍的核心位置,而非视为化学或生化线索的附属因素。基于基础细胞迁移生物学和近期工程学进展,我们强调,设计具有明确几何特征的微流控装置能够独特地捕捉限域对免疫细胞行为的影响,并用于模拟这一挑战。通过精准控制孔径、通道几何形状和仿生结构,这些平台可使研究者将限域效应与刚度等其他相互重叠的变量区分开来。
Chimeric antigen receptor (CAR) T-cell migration and infiltration into solid tumours remains a central challenge for cancer immunotherapy. While factors such as chemokine gradients, extracellular matrix (ECM) stiffness, and immunosuppressive signalling have been well-documented, the physical confinement imposed by tumour architecture is increasingly recognized as a critical barrier. Tumour-associated ECM remodelling generates micro- and nano-scale geometric constraints that significantly alter how immune cells, particularly CAR T-cells, navigate the tumour microenvironment (TME).
This article argues that physical confinement merits to be positioned at the centre of the migration challenge, not as an accessory to chemical or biochemical cues. Sustained from both fundamental cell migration biology and recent engineering advances, we highlight how designing microfluidic devices with defined geometric features can uniquely capture the role of confinement in immune cell behaviour and model this challenge.
By enabling precise design control over pore size, channel geometry, and nature-inspired structures, these platforms will allow researchers to decouple confinement from other overlapping variables such as stiffness.
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