在过去的两个世纪里，对组织环境中的细胞进行显微镜检查一直是诊断组织病理学背后的驱动力。最近，通过单细胞分析鉴定的先进分子生物标志物的兴起增加了我们对癌症细胞异质性的理解，但尚未对临床护理产生重大影响。将分子分析与微环境特征相结合的空间技术有望通过提供理解细胞相互作用和组织的关键原位环境来弥补这一转化差距。在这里，我们回顾了如何使用空间工具来研究肿瘤生态系统及其临床应用。我们详细介绍了细胞间相互作用、微环境组成以及免疫逃避和治疗抵抗的组织重塑方面的发现。此外，我们强调了多组学空间分析在表征临床相关特征（包括神经周围浸润、三级淋巴结构和肿瘤间质界面）方面的新兴作用。最后，我们探索临床整合策略及其增强治疗和诊断方法。版权所有 © 2024 Elsevier Inc. 保留所有权利。

Microscopic examination of cells in their tissue context has been the driving force behind diagnostic histopathology over the past two centuries. Recently, the rise of advanced molecular biomarkers identified through single cell profiling has increased our understanding of cellular heterogeneity in cancer but have yet to significantly impact clinical care. Spatial technologies integrating molecular profiling with microenvironmental features are poised to bridge this translational gap by providing critical in situ context for understanding cellular interactions and organization. Here, we review how spatial tools have been used to study tumor ecosystems and their clinical applications. We detail findings in cell-cell interactions, microenvironment composition, and tissue remodeling for immune evasion and therapeutic resistance. Additionally, we highlight the emerging role of multi-omic spatial profiling for characterizing clinically relevant features including perineural invasion, tertiary lymphoid structures, and the tumor-stroma interface. Finally, we explore strategies for clinical integration and their augmentation of therapeutic and diagnostic approaches.Copyright © 2024 Elsevier Inc. All rights reserved.