Single-cell insights into tumor microenvironment heterogeneity and plasticity: transforming precision therapy in gastrointestinal cancers
Jialei Weng, Feng Ju, Zicheng Lyu, Ningbo Fan, Daniel J. Smit, Wenxin Xu, Xiao‐Lin Wu, Philip Becker, Yinan Xu, Michal R. Schweiger, Axel M. Hillmer, Ralf Harwig, Sheraz Gul, Alexander Link, Lydia Meder, Nan Fang, Qiongzhu Dong, Christiane J. Bruns, Ning Ren, Yue Zhao
Abstract
The development and progression of gastrointestinal (GI) cancers not only depend on the malignancy of the tumor cells, but is also defined by the complex and adaptive nature of the tumor microenvironment (TME). The TME in GI cancers exhibits a complex internal structure, typically comprising cancer cells, cancer stem cells, cancer-associated fibroblasts, immune cells, and endothelial cells, all embedded within a dynamic extracellular matrix. This intricate ecosystem fuels tumor initiation, progression, metastasis, recurrence and therapy response through the heterogeneity and plasticity. Recent advances in single-cell sequencing have provided unprecedented resolution in profiling the cellular diversity and interactions within the TME. These technologies have uncovered previously unknown cell subtypes and intricate communication networks that drive therapy resistance and tumor relapse. In this review, we summarize and discuss the latest findings from single-cell sequencing of key cellular players and their interactions within the TME of GI cancers. We highlight single cell insights that are reshaping our understanding of tumor biology, with particular focus on their implications for overcoming therapy resistance and improving clinical outcomes. We believe that a deeper understanding of TME heterogeneity and plasticity at the single-cell level promises to transform the landscape of precision treatment in GI cancers.