June 25, 2026
A first-of-its-kind blood test may help oncologists better predict which patients will benefit from immunotherapy.
Researchers from Mayo Clinic and Stanford Medicine, who published their findings in Nature in 2026, describe the development as the first blood test capable of noninvasively mapping the tumor microenvironment — a breakthrough that introduces a new method for profiling the biological "neighborhoods" surrounding tumors using a blood sample rather than tissue biopsy.
"This is a complete paradigm shift," says Aadel A. Chaudhuri, M.D., Ph.D., co-senior author of the study and a radiation oncologist at Mayo Clinic in Rochester, Minnesota. "Until now, liquid biopsies or blood tests have focused almost entirely on tumor cells. For the first time, we can use a simple test to understand the tumor's microenvironment, which is critical for determining how patients respond to modern cancer therapies."
Understanding the tumor ecosystem
As immunotherapy and targeted therapies continue to reshape oncology care, researchers have increasingly focused on the tumor microenvironment — the ecosystem of immune cells, stromal cells and surrounding tissue that can influence how cancers grow and respond to treatment.
But evaluating these interactions has historically required tissue sampling, which offers only a limited snapshot of a dynamic biological process.
In this study, investigators developed a blood-based approach capable of recognizing spatial ecotypes, which are recurring cellular ecosystems, also called tumor neighborhoods, shared across multiple cancer types.
Researchers used spatial transcriptomics to map how different cells interact within a tumor. They identified nine distinct spatial ecotypes, each representing a unique immune and stromal environment.
Investigators found that all 17 tested cancer types share these neighborhoods. While some are more likely to occur at the border of the tumor and healthy tissue, others are more likely to be found deeper inside the tumor.
"Almost like geographic mapping, we were able to map where in the tumor microenvironment these neighborhoods of co-associated cells live," Dr. Chaudhuri explains. "Then, we showed that certain neighborhoods, or spatial ecotypes, are associated with survival and immunotherapy response outcomes."
Next, researchers developed an artificial intelligence framework capable of detecting these ecotypes through methylation patterns in cell-free DNA shed into the bloodstream. The result was a liquid biopsy test that profiles the tumor microenvironment beyond the cancer cells themselves.
"This is the first time we've been able to noninvasively profile the tumor microenvironment at this level," Dr. Chaudhuri says.
Potential implications for cancer care
In studies involving more than 1,300 patients across multiple cancers — including melanoma and lung, bladder and gastric cancers — specific spatial ecotypes were strongly associated with treatment outcomes. Certain ecotypes were predicted to respond positively to immunotherapy, while others were linked to treatment resistance and poorer survival. Standard biomarkers demonstrated inferior predictive power.
Researchers say this new test could eventually help clinicians make more-informed treatment decisions and monitor tumor biology over time.
"If a patient isn't going to respond, that's time we could be using a different treatment," Dr. Chaudhuri says. "Better upfront decision-making can directly improve outcomes."
Because the test is blood based, investigators also believe it may offer a dynamic way to monitor how cancers evolve during therapy.
"This gives us a window into how the tumor microenvironment is changing over time," Dr. Chaudhuri says. "We've never been able to see that before in a practical way."
What's next for tumor microenvironment profiling
Although the technology remains investigational, researchers say the findings establish proof of concept for noninvasive tumor microenvironment profiling and could help lay the groundwork for future blood-based tools that personalize cancer treatment strategies.
The research team is continuing to validate the test in larger patient populations and explore how spatial ecotypes may predict response to therapies beyond immunotherapy.
"This work opens up an entirely new way of thinking about disease," Dr. Chaudhuri says. "We've essentially uncovered a world that was invisible to us before — and now we can access it with a simple blood test."
For more information
Zhang W, et al. Non-invasive profiling of the tumour microenvironment with spatial ecotypes. Nature. In press.
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