Cancer and Stem Cell Biology Programme, Duke-NUS Medical School, Singapore 169857, Singapore.
Division of Medical Oncology, National Cancer Centre Singapore, Singapore 168583, Singapore.
Cells. 2023 Apr 14;12(8):1165. doi: 10.3390/cells12081165.
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.
自上个世纪初以来，细胞介导免疫方面的里程碑式发现使人们对先天和适应性免疫系统有了更深入的了解，并彻底改变了无数疾病的治疗方法，包括癌症。如今，精准免疫肿瘤学（IO）不仅涉及针对抑制 T 细胞免疫的免疫检查点，还涉及利用免疫细胞疗法。一些癌症的疗效有限，主要是由于肿瘤微环境（TME）复杂，除了适应性免疫细胞外，还包括先天髓样和淋巴样细胞、癌相关成纤维细胞以及有助于免疫逃逸的肿瘤血管。由于 TME 的复杂性需要更复杂的基于人类的肿瘤模型，类器官使人们能够动态研究肿瘤细胞与单个 TME 细胞类型之间的时空相互作用。在这里，我们讨论了类器官如何在癌症中研究 TME，以及这些特征如何提高精准 IO 的效果。我们概述了在肿瘤类器官中保留或再现 TME 的方法，并讨论了它们的潜力、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确定新的 IO 靶点和治疗策略方面的未来方向。
