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Non-invasive profiling of the tumour microenvironment with spatial ecotypes

NatureResearch Authors: Wubing Zhang, Erin L. Brown, Abul Usmani, Noah Earland, Minji Kang, Chibuzor Olelewe, Anushka Viswanathan, Pradeep S. Chauhan, Chloé B. Steen, Hyun Soo Jeon, Susanna Avagyan, Irfan Alahi, Nicholas P. Semenkovich, Janella C. Schwab, Chloe M. Sachs, Faridi Qaium, Peter K. Harris, Qingyuan Cai, Andrew J. Gentles, James Knight, Rondell P. Graham, Antonietta Bacchiocchi, Peter C. Lucas, Ryan C. Fields, Mario Sznol, Ruth Halaban, David Y. Chen, Aadel A. Chaudhuri and Aaron M. NewmanAIIM Authors: Natasha Kejriwal, Annika KumarApproved by President Reda RiffiPublication Date: 5/6/2026

Comprehensive Summary

This study used a machine-learning framework to identify spatial ecotypes, which are recurring multicellular ecosystems within a tumor’s microenvironment defined by spatial organization of cells and their abundances. The researchers analyzed millions of single-cell and spatial gene expression profiles across different cancers and identified nine ecotypes with several conserved, predictive features. The authors also developed tools that can detect these ecotypes not only in tumor tissue, but also from cell-free DNA extracted from plasma. Some ecotypes were linked to stronger immune responses, while others were connected to tumor growth and worse clinical outcomes.

Outcomes and Implications

The use of spatial ecotypes has significant clinical implications for how doctors predict a patient's response to cancer treatments. Specific ecotypes were found to be strong indicators of whether a patient would benefit from immunotherapy. This technology offers a less invasive way to characterize a tumor as well as the response to therapy over time. Physicians may be able to analyze tumors using blood samples, making testing easier for patients. This framework could lead to more personalized medicine by helping to select the most effective therapies based on a tumor’s cell composition, making the approach useful for individual cancer care.

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