Single-cell insights into tumor microenvironment heterogeneity and plasticity: transforming precision therapy in gastrointestinal cancers
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.
Authors
- Daniel J. Smit (ORCID: https://orcid.org/0000-0002-3190-9511)
- Yinan Xu (ORCID: https://orcid.org/0000-0002-2013-8803)
- Qiongzhu Dong (ORCID: https://orcid.org/0000-0002-2433-7199)
- Jialei Weng (ORCID: https://orcid.org/0000-0002-4916-0799)
- Ningbo Fan (ORCID: https://orcid.org/0000-0002-1622-6747)
- Wenxin Xu (ORCID: https://orcid.org/0009-0007-7312-4302)
- Axel M. Hillmer (ORCID: https://orcid.org/0000-0002-3381-7266)
- Christiane J. Bruns (ORCID: https://orcid.org/0000-0001-6590-8181)
- Sheraz Gul (ORCID: https://orcid.org/0000-0003-2543-1643)
- Lydia Meder (ORCID: https://orcid.org/0000-0002-9547-5812)
- Piet Becker (ORCID: https://orcid.org/0000-0002-9384-6472)
- Michal R. Schweiger (ORCID: https://orcid.org/0000-0002-4672-0623)
- Yue Zhao (ORCID: https://orcid.org/0000-0001-5544-5697)
- Feng Ju (ORCID: https://orcid.org/0000-0001-6311-6551)
- Nan Fang (ORCID: https://orcid.org/0000-0001-6234-8932)
- Xiao‐Lin Wu (ORCID: https://orcid.org/0000-0002-5604-9220)
- Zejian Lyu
- Ning Ren (ORCID: https://orcid.org/0009-0001-5240-1899)
- Alexander Link (ORCID: https://orcid.org/0009-0004-0545-3161)
- Ralf Harwig
Institutions
- Universität Hamburg (DE)
- University of Cologne (DE)
- Friedrich-Alexander-Universität Erlangen-Nürnberg (DE)
- Fraunhofer Institute for Translational Medicine and Pharmacology (DE)
- University Medical Center Hamburg-Eppendorf (DE)
- Singleron Biotechnologies (china) (CN)
- Shanghai Municipal Commission of Health and Family Planning (CN)
- Max Planck Institute for Molecular Genetics (DE)
- Ministry of Education (ET)
- University Hospital Cologne (DE)
- Shanghai Municipal Education Commission (CN)
Publication Details
- Journal
- Journal of Experimental & Clinical Cancer Research
- Published
- 2025-11-28
- DOI
- https://doi.org/10.1186/s13046-025-03567-5
- Citations
- 4
- Primary Topic
- Single-cell and spatial transcriptomics
- Type
- article
- Field-Weighted Citation Impact
- 3.22