Researchers at Mayo Clinic and Stanford Medicine have developed the first blood test capable of mapping the complex ecosystem, or ‘neighborhoods,’ surrounding cancer cells. This novel liquid biopsy approach, detailed in the May 6, 2026, online edition of Nature, represents a significant advance in precision oncology—offering clinicians a more accurate tool for predicting which patients will benefit from immunotherapy and potentially guiding treatment decisions across multiple cancer types.
Paradigm Shift in Tumor Microenvironment Profiling
“Until now, liquid biopsies or blood tests have focused almost entirely on tumor cells,” said Aadel Chaudhuri, M.D., Ph.D., professor of radiation oncology at Mayo Clinic and co-senior author of the study.
“For the first time, we can use a simple blood test to understand the tumor’s microenvironment, which is critical for determining how patients respond to modern cancer therapies,” Chaudhuri added
Immunotherapy has revolutionized cancer care but remains effective for only a subset of patients. Conventional predictive tools—such as DNA mutation load or protein expression on cancer cells—fall short of capturing the intricate dynamics within the tumor microenvironment (TME).
Mapping the Tumor Ecosystem: Spatial Ecotypes
The research team leveraged spatial transcriptomics, an advanced technique that maps how different cells interact within a tumor, to identify nine distinct cellular neighborhoods, or spatial ecotypes. These ecotypes—conserved across 17 cancer types—represent unique immune and stromal landscapes. Certain ecotypes are associated with improved survival and positive immunotherapy responses, while others correlate with resistance and poorer outcomes.
Using artificial intelligence (AI) and methylation profiling of cell-free DNA (cfDNA) shed into the bloodstream, the researchers developed a blood test that noninvasively profiles these spatial ecotypes.
“Almost like geographic mapping, we were able to map where these neighborhoods exist within the tumor microenvironment. Specific ecotypes can predict survival and response to immunotherapy,” explained Chaudhuri
Clinical Impact: Improving Treatment Decisions and Real-Time Monitoring
In a study spanning more than 1,300 patients across multiple cancer types—including melanoma, lung, bladder, and gastric cancers—specific spatial ecotypes strongly predicted treatment outcomes. The new blood test outperformed standard biomarkers in forecasting immunotherapy response.
The ability to predict therapy response before treatment could have an immediate clinical impact, sparing patients ineffective and potentially toxic therapies.
“If a patient isn’t going to respond, that’s a time we could be using a different treatment,” Chaudhuri noted. Personalized spatial ecotype profiles may also help clinicians select therapies most suited to individual tumor biology.
Because the test is blood-based, it enables ongoing monitoring of how a tumor’s microenvironment evolves during treatment. Early data suggest changes in spatial ecotypes can signal response or resistance months before traditional imaging methods.
Expanding Beyond Cancer: Insights Into Complex Diseases
While initial studies focused on melanoma, the approach shows promise for a broad range of cancers, including lung and bladder cancer, and for predicting responses to other therapies, such as antibody drug conjugates. The researchers believe their technology may eventually extend beyond oncology, offering insights into complex biological environments underlying diverse diseases.
Future Directions
Further studies are underway to validate the test in larger patient populations and expand its use in clinical practice. Researchers are also exploring how different spatial ecotype patterns may predict response to therapies beyond immunotherapy.
“This work opens up an entirely new way of thinking about disease. We’ve essentially uncovered a world that was invisible to us before—and now we can access it with a simple blood test,” Chaudhuri concluded.
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Disclosures: Aadel Chaudhuri, M.D., Ph.D., and Aaron Newman, Ph.D., have patent filings and ownership interests related to liquid biopsy and cancer biomarkers.
Reference
[1] Zhang W, Brown EL, Usmani A, Earland N, Kang M, Olelewe C, Viswanathan A, Chauhan PS, Steen CB, Jeon HS, Avagyan S, Alahi I, Semenkovich NP, Schwab JC, Sachs CM, Qaium F, Harris PK, Cai Q, Gentles AJ, Knight J, Graham RP, Bacchiocchi A, Lucas PC, Fields RC, Sznol M, Halaban R, Chen DY, Chaudhuri AA, Newman AM. Non-invasive profiling of the tumour microenvironment with spatial ecotypes. Nature (2026). https://doi.org/10.1038/s41586-026-10452-4 [Download PDF]
Featured image: © 2020 – 2026 Solen Feyissa on Unsplash. Used with permission.
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