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Peer-reviewedCC BYCell Discovery

Spatial single-cell landscape of tumor-associated macrophages and their crosstalk with the tumor microenvironment

9 affiliations
  1. 1Fujian Provincial Key Laboratory of Innovative Drug Target Research, School of Pharmaceutical Sciences, Faculty of Medicine and Life Sciences, Xiamen University, Xiamen, Fujian, China
  2. 2National Institute for Data Science in Health and Medicine, Xiamen University, Xiamen, Fujian, China
  3. 3State Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, School of Pharmaceutical Sciences, Faculty of Medicine and Life Sciences, Xiamen University, Xiamen, Fujian, China
  4. 4Biomedical Research Center of South China, College of Life Sciences, Fujian Normal University, Fuzhou, Fujian, China
  5. 5Department of Thoracic Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian, China
  6. 6Fujian Provincial Key Laboratory of Innovative Drug Target Research, School of Pharmaceutical Sciences, Faculty of Medicine and Life Sciences, Xiamen University, Xiamen, Fujian, China. [email protected]
  7. 7National Institute for Data Science in Health and Medicine, Xiamen University, Xiamen, Fujian, China. [email protected]
  8. 8Shenzhen Research Institute of Xiamen University, Shenzhen, China. [email protected]
  9. 9State Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, School of Pharmaceutical Sciences, Faculty of Medicine and Life Sciences, Xiamen University, Xiamen, Fujian, China. [email protected]

Abstract

Tumor-associated macrophages (TAMs) constitute a critical immune cell population within the tumor microenvironment (TME) and exhibit high functional heterogeneity. In this study, a pan-cancer atlas comprising 28 TAM subtypes was systematically constructed by integrating single-cell transcriptomic and spatial transcriptomic data from 291 human samples across 16 cancer types. The biological characteristics and spatial distribution patterns of these subtypes within the TME as well as the interaction mechanisms between TAMs and TME components closely associated with tumor progression were elucidated. TAMs localized in the peritumoral or core regions of tumors participate in angiogenesis and metabolic reprogramming, promoting further tumor development. The retention of CD8 + T cells by TAMs can induce local inflammation and an immunosuppressive microenvironment. Additionally, cancer-associated fibroblasts (CAFs) play crucial roles in the polarization and survival of TAMs and are involved in their recruitment and activation. TAMs facilitate tumor invasion, metastasis and immune evasion through secreted phosphoprotein 1 (SPP1) and interaction with the integrin family/CD44 axis in CAFs. This study deepens the understanding of the biological characteristics of TAMs and provides new theoretical foundations and potential targets for cancer treatment strategies targeting specific TAM subpopulations.

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BibTeX
@article{nie2026spatial,
  title = {{Spatial single-cell landscape of tumor-associated macrophages and their crosstalk with the tumor microenvironment}},
  author = {Rui-chao Nie and Guosheng Hu and Shi-qiang Cao and An Wang and Du-chuang Wang and Wen Liu},
  journal = {Cell Discovery},
  year = {2026},
  month = may,
  doi = {10.1038/s41421-026-00888-3},
  url = {https://doi.org/10.1038/s41421-026-00888-3},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - Spatial single-cell landscape of tumor-associated macrophages and their crosstalk with the tumor microenvironment
AU  - Rui-chao Nie
AU  - Guosheng Hu
AU  - Shi-qiang Cao
AU  - An Wang
AU  - Du-chuang Wang
AU  - Wen Liu
PY  - 2026
DA  - 2026/05/19
JO  - Cell Discovery
DO  - 10.1038/s41421-026-00888-3
UR  - https://doi.org/10.1038/s41421-026-00888-3
AB  - Tumor-associated macrophages (TAMs) constitute a critical immune cell population within the tumor microenvironment (TME) and exhibit high functional heterogeneity. In this study, a pan-cancer atlas comprising 28 TAM subtypes was systematically constructed by integrating single-cell transcriptomic and spatial transcriptomic data from 291 human samples across 16 cancer types. The biological characteristics and spatial distribution patterns of these subtypes within the TME as well as the interaction mechanisms between TAMs and TME components closely associated with tumor progression were elucidated. TAMs localized in the peritumoral or core regions of tumors participate in angiogenesis and metabolic reprogramming, promoting further tumor development. The retention of CD8 + T cells by TAMs can induce local inflammation and an immunosuppressive microenvironment. Additionally, cancer-associated fibroblasts (CAFs) play crucial roles in the polarization and survival of TAMs and are involved in their recruitment and activation. TAMs facilitate tumor invasion, metastasis and immune evasion through secreted phosphoprotein 1 (SPP1) and interaction with the integrin family/CD44 axis in CAFs. This study deepens the understanding of the biological characteristics of TAMs and provides new theoretical foundations and potential targets for cancer treatment strategies targeting specific TAM subpopulations.
SN  - 2056-5968
ER  -