CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Organoids as an Enabler of Precision Immuno-Oncology.
Organoids as an Enabler of Precision Immuno-Oncology.
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自上世纪之初以来,细胞介导免疫领域的里程碑式发现使人们对固有免疫和适应性免疫系统有了更深入的理解,并彻底改变了包括癌症在内的无数疾病的治疗。如今,精准免疫肿瘤学(I/O)不仅涉及靶向抑制T细胞免疫的免疫检查点,还包括利用免疫细胞疗法。某些癌症中疗效有限主要源于复杂的肿瘤微环境(TME),该微环境除适应性免疫细胞外,还包括固有髓系和淋巴系细胞、癌症相关成纤维细胞以及肿瘤血管系统,这些成分共同促进免疫逃逸。由于TME的复杂性需要更精密的人源肿瘤模型,类器官使得研究肿瘤细胞与TME各细胞类型之间的时空相互作用动态成为可能。在此,我们讨论类器官如何跨癌种研究TME,以及这些特征如何可能改善精准I/O。我们概述了在肿瘤类器官中保留或重建TME的方法,并讨论其潜力、优势和局限性。我们将讨论类器官研究在深入理解癌症免疫学以及识别新型I/O靶点和治疗策略方面的未来方向。
Since the dawn of the past century, landmark discoveries in cell-mediated immunity have led to a greater understanding of the innate and adaptive immune systems and revolutionised the treatment of countless diseases, including cancer. Today, precision immuno-oncology (I/O) involves not only targeting immune checkpoints that inhibit T-cell immunity but also harnessing immune cell therapies.
The limited efficacy in some cancers results mainly from a complex tumour microenvironment (TME) that, in addition to adaptive immune cells, comprises innate myeloid and lymphoid cells, cancer-associated fibroblasts, and the tumour vasculature that contribute towards immune evasion. As the complexity of TME has called for more sophisticated human-based tumour models, organoids have allowed the dynamic study of spatiotemporal interactions between tumour cells and individual TME cell types.
Here, we discuss how organoids can study the TME across cancers and how these features may improve precision I/O.
We outline the approaches to preserve or recapitulate the TME in tumour organoids and discuss their potential, advantages, and limitations.
We will discuss future directions of organoid research in understanding cancer immunology in-depth and identifying novel I/O targets and treatment strategies.
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