Gohil Satyen H, Iorgulescu J Bryan, Braun David A, Keskin Derin B, Livak Kenneth J
Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Department of Academic Haematology, University College London Cancer Institute, London, UK.
Nat Rev Clin Oncol. 2021 Apr;18(4):244-256. doi: 10.1038/s41571-020-00449-x. Epub 2020 Dec 4.
Advances in molecular biology, microfluidics and bioinformatics have empowered the study of thousands or even millions of individual cells from malignant tumours at the single-cell level of resolution. This high-dimensional, multi-faceted characterization of the genomic, transcriptomic, epigenomic and proteomic features of the tumour and/or the associated immune and stromal cells enables the dissection of tumour heterogeneity, the complex interactions between tumour cells and their microenvironment, and the details of the evolutionary trajectory of each tumour. Single-cell transcriptomics, the ability to track individual T cell clones through paired sequencing of the T cell receptor genes and high-dimensional single-cell spatial analysis are all areas of particular relevance to immuno-oncology. Multidimensional biomarker signatures will increasingly be crucial to guiding clinical decision-making in each patient with cancer. High-dimensional single-cell technologies are likely to provide the resolution and richness of data required to generate such clinically relevant signatures in immuno-oncology. In this Perspective, we describe advances made using transformative single-cell analysis technologies, especially in relation to clinical response and resistance to immunotherapy, and discuss the growing utility of single-cell approaches for answering important research questions.
分子生物学、微流控技术和生物信息学的进展，使得在单细胞分辨率水平上对恶性肿瘤中的数千甚至数百万个单个细胞进行研究成为可能。对肿瘤和/或相关免疫及基质细胞的基因组、转录组、表观基因组和蛋白质组特征进行这种高维度、多方面的表征，能够剖析肿瘤异质性、肿瘤细胞与其微环境之间的复杂相互作用，以及每个肿瘤进化轨迹的细节。单细胞转录组学、通过T细胞受体基因的配对测序追踪单个T细胞克隆的能力以及高维度单细胞空间分析，都是与免疫肿瘤学特别相关的领域。多维生物标志物特征对于指导每位癌症患者的临床决策将变得越来越关键。高维度单细胞技术可能会提供在免疫肿瘤学中生成此类临床相关特征所需的数据分辨率和丰富度。在本观点文章中，我们描述了使用变革性单细胞分析技术所取得的进展，特别是与临床反应和免疫治疗耐药性相关的进展，并讨论了单细胞方法在回答重要研究问题方面日益增长的效用。
