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:Microfluidic chips for decoding cancer-immune crosstalk in immunotherapy.
Microfluidic chips for decoding cancer-immune crosstalk in immunotherapy.
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肿瘤微环境(TME)中癌细胞与免疫系统之间的相互作用决定免疫治疗干预的效果,但传统临床前模型无法重现这些动态过程。微生理系统,尤其是具有免疫功能的肿瘤芯片(TOC)平台,弥合了简化二维培养与动物模型之间的差距。这些装置整合微流控工程、仿生细胞外基质和受控灌流,可有效重现TME的细胞异质性、三维结构和生理流动条件。本综述考察具有免疫功能的TOC平台的工程原理及其在癌症免疫治疗研究中的应用。这些系统可对癌症免疫循环开展机制研究,包括免疫细胞募集、迁移和肿瘤细胞细胞毒性。它们对于评估CAR-T 细胞等细胞免疫疗法尤其有价值,也可用于药物筛选和联合治疗测试。与患者来源细胞整合后,TOC平台有望用于功能性精准肿瘤学。近期进展提升了模型的生理复杂度,例如多器官芯片系统可捕捉全身相互作用,淋巴结芯片可用于研究免疫激活,器官特异性模型则可模拟转移部位。尽管潜力巨大,标准化、临床验证以及实验复杂性与可控性之间的平衡仍是挑战。随着该领域通过协作和先进分析技术整合来解决这些局限,具有免疫功能的TOC平台有望成为理解癌症-免疫生物学和加速个体化免疫治疗的重要工具。
The crosstalk between cancer cells and the immune system within the tumor microenvironment (TME) governs the efficacy of immunotherapeutic interventions.
However, conventional preclinical models fail to recapitulate these dynamic processes. Microphysiological systems, particularly immunocompetent tumor-on-a-chip (TOC) platforms, bridge the gap between simplified two-dimensional cultures and animal models. These devices integrate microfluidic engineering, biomimetic extracellular matrices, and controlled perfusion. These platforms effectively recapitulate the cellular heterogeneity, three-dimensional structure, and physiological flow conditions of the TME. This review examines the engineering principles of immunocompetent TOC platforms and their applications in cancer immunotherapy research. These systems enable mechanistic studies of the cancer-immunity cycle, including immune cell recruitment, migration, and tumor cell cytotoxicity. They are particularly valuable for evaluating cell-based immunotherapies, including CAR-T cells.
TOC platforms also facilitate drug screening and the testing of combination therapies. They show promise for functional precision oncology when integrated with patient-derived cells. Recent advances have extended these models toward greater physiological complexity. For example, multi-organ-on-a-chip systems capture systemic interactions, while lymph node-on-a-chip platforms enable studies of immune activation, and additionally organ-specific models mimic metastatic sites.
Despite their potential, challenges remain in standardization, clinical validation, and balancing complexity with experimental control. As the field addresses these limitations through collaboration and integration with advanced analytics, immunocompetent TOC platforms are poised to become essential tools for understanding cancer-immune biology and accelerating personalized immunotherapy.
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