Sinjab Ansam, Rahal Zahraa, Kadara Humam
Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Cancers (Basel). 2022 Jul 14;14(14):3424. doi: 10.3390/cancers14143424.
For lung cancers, cellular trajectories and fates are strongly pruned by cell intrinsic and extrinsic factors. Over the past couple of decades, the combination of comprehensive molecular and genomic approaches, as well as the use of relevant pre-clinical models, enhanced micro-dissection techniques, profiling of rare preneoplastic lesions and surrounding tissues, as well as multi-region tumor sequencing, have all provided in-depth insights into the early biology and evolution of lung cancers. The advent of single-cell sequencing technologies has revolutionized our ability to interrogate these same models, tissues, and cohorts at an unprecedented resolution. Single-cell tracking of lung cancer pathogenesis is now transforming our understanding of the roles and consequences of epithelial-microenvironmental cues and crosstalk during disease evolution. By focusing on non-small lung cancers, specifically lung adenocarcinoma subtype, this review aims to summarize our knowledge base of tumor cells-of-origin and tumor-immune dynamics that have been primarily fueled by single-cell analysis of lung adenocarcinoma specimens at various stages of disease pathogenesis and of relevant animal models. The review will provide an overview of how recent reports are rewriting the mechanistic details of lineage plasticity and intra-tumor heterogeneity at a magnified scale thanks to single-cell studies of early- to late-stage lung adenocarcinomas. Future advances in single-cell technologies, coupled with analysis of minute amounts of rare clinical tissues and novel animal models, are anticipated to help transform our understanding of how diverse micro-events elicit macro-scale consequences, and thus to significantly advance how basic genomic and molecular knowledge of lung cancer evolution can be translated into successful targets for early detection and prevention of this lethal disease.
对于肺癌而言，细胞内在和外在因素会强烈地塑造细胞轨迹和命运。在过去几十年里，综合分子和基因组方法的结合，以及相关临床前模型的使用、增强的显微切割技术、罕见癌前病变及其周围组织的分析，还有多区域肿瘤测序，都为深入了解肺癌的早期生物学特性和演变提供了见解。单细胞测序技术的出现彻底改变了我们以前所未有的分辨率研究这些模型、组织和队列的能力。肺癌发病机制的单细胞追踪正在改变我们对疾病演变过程中上皮-微环境信号及相互作用的作用和后果的理解。通过聚焦于非小细胞肺癌，特别是肺腺癌亚型，本综述旨在总结我们关于肿瘤起源细胞和肿瘤-免疫动力学的知识基础，这些主要是由对疾病发病机制不同阶段的肺腺癌标本及相关动物模型的单细胞分析推动的。该综述将概述近期报告如何借助对早期至晚期肺腺癌的单细胞研究，在更大规模上重写谱系可塑性和肿瘤内异质性的机制细节。预计单细胞技术的未来进展，再加上对微量罕见临床组织和新型动物模型的分析，将有助于改变我们对各种微观事件如何引发宏观后果的理解，从而显著推动肺癌演变的基础基因组和分子知识转化为这种致命疾病早期检测和预防的成功靶点。
