Resolving the spatial and cellular architecture of intra-tumor heterogeneity by multi-region dissection of lung adenocarcinoma
Although the spatial characteristics within the tumor microenvironment of lung adenocarcinoma (LUAD) have been identified, the mechanisms by which these factors promote LUAD progression and immune evasion remain unclear. Using spatial transcriptomics and single-cell RNA-sequencing data from multi-regional LUAD biopsies consisting of tumor core, tumor edge, and normal area, we sought to delineate the spatial heterogeneity and driving factors of cell colocalization. Two cancer cell sub-clusters (Cancer_c1 and Cancer_c2), associated with LUAD initiation and metastasis, respectively, exhibit distinct spatial distributions and immune cell colocalizations. In particular, Cancer_c1, enriched within the tumor core, could directly interact with B cells or indirectly recruit B cells through macrophages. Conversely, Cancer_c2 enriched within the tumor edge exhibits colocalization with CD8<sup>+</sup> T cells. Collectively, our work elucidates the spatial distribution of cancer cell subtypes and their interaction with immune cells in the core and edge of LUAD, providing insights for developing therapeutic strategies for cancer intervention.
Authors
- Tianning Wang (ORCID: https://orcid.org/0000-0003-3430-6975)
- Yuanhui Ma (ORCID: https://orcid.org/0000-0003-0868-3160)
- Mingming Su (ORCID: https://orcid.org/0000-0002-9996-9094)
- Yanhua Wu (ORCID: https://orcid.org/0000-0002-2803-809X)
- Xu Wang (ORCID: https://orcid.org/0000-0003-1060-840X)
- Zheng Yan (ORCID: https://orcid.org/0000-0001-9324-2161)
- Peng Zhang (ORCID: https://orcid.org/0000-0002-6218-1885)
- Xiaolei Wang (ORCID: https://orcid.org/0000-0001-9431-0058)
- Xinlei Zhang (ORCID: https://orcid.org/0000-0002-9270-0527)
- Ying Huang (ORCID: https://orcid.org/0000-0002-4627-1661)
- Jingnan Wang (ORCID: https://orcid.org/0000-0002-3165-6876)
- Mengmeng Zhao (ORCID: https://orcid.org/0000-0002-9682-6450)
- Qing Huang (ORCID: https://orcid.org/0000-0001-8393-2003)
- Song Mei (ORCID: https://orcid.org/0009-0005-0426-2467)
- Xueyu Hao
Institutions
- Fujian Medical University (CN)
- Shandong University (CN)
- Capital Medical University (CN)
- Jinan Central Hospital (CN)
- Shandong Mental Health Center (CN)
- Beijing Children’s Hospital (CN)
- Cloud Computing Center (CN)
- Shanghai Children's Hospital (CN)
- Shandong First Medical University (CN)
Publication Details
- Journal
- Journal of genetics and genomics/Journal of Genetics and Genomics
- Published
- 2025-02-22
- DOI
- https://doi.org/10.1016/j.jgg.2025.02.006
- Citations
- 2
- Primary Topic
- Single-cell and spatial transcriptomics
- Type
- article
- Field-Weighted Citation Impact
- 1.61
Funders
- National Natural Science Foundation of China