LiquidCell Dx, a next generation cancer diagnostics company, today announced publication in Nature of critical research underpinning the development of LiquidTME, its blood-based assay for tumor microenvironment profiling. The paper defines highly recurrent and clinically relevant features of the tumor microenvironment, including the immune cells, but also the many other cell types present in a tumor and their key functions, and demonstrates that they can be measured from a standard blood draw. This allows the tumor microenvironment, which strongly modulates cancer therapy response, to be accessed in a noninvasive manner.
The Nature paper, led by senior authors Aaron M. Newman, PhD, of Stanford University and Aadel A. Chaudhuri, MD, PhD, of Mayo Clinic, together with collaborators across Stanford, Mayo Clinic, Washington University, Yale, and other institutions, identified nine recurring multicellular ecosystems in and around solid tumors, called spatial ecotypes, and showed that they can be detected from plasma cell-free DNA using artificial intelligence.
The paper integrated over 10 million single-cell and spot-level spatial transcriptomes from 132 tumor specimens across 10 malignancies to identify these recurring ecosystems, each with distinct biology, geospatial features, and clinical outcome associations. The authors then showed that these ecotypes are distinguishable by DNA methylation profiling and recoverable from plasma cell-free (cf) DNA using a noninvasive blood draw, completely obviating the need for a tumor biopsy. In nearly 100 melanoma patients, plasma-derived spatial ecotype levels obtained prior to treatment initiation showed strong associations with immunotherapy response and survival.
LiquidTME is LiquidCell Dx’s blood-based, noninvasive assay that builds on and extends that work. Where the Nature paper demonstrates that the discovered ecotypes can accurately predict immunotherapy response in melanoma, LiquidCell Dx is applying that work to build a blood-based test that informs treatment decisions across cancer types and treatment modalities. Since the work described in the paper, LiquidCell Dx has continued to advance the assay toward clinical and commercial development.
At the American Association for Cancer Research (AACR) Annual Meeting 2026, LiquidCell Dx and collaborators presented a blinded clinical validation of LiquidTME in metastatic melanoma. In a Washington University cohort of 34 patients treated with combination immune checkpoint inhibitors, a current standard of care, LiquidTME identified durable responders from pretreatment plasma and maintained whole-cohort performance in patients with available tumor mutational burden (TMB) data, a measurement currently widely used in clinical decision making. In contrast, TMB high versus low measurement failed to significantly stratify response or progression-free survival in the same group. The AACR poster concluded that LiquidTME shows strong generalizability and promise as a clinical tool to guide personalized immunotherapy decision-making, and that performance in an independent, blinded cohort supports the robustness of the platform beyond the discovery dataset.
“Cancer treatment is still too often shaped by partial information,” said Mirna Jarosz, PhD, Chief Executive Officer of LiquidCell Dx. “We can read the tumor itself with far greater precision than a decade ago, yet that still does not tell us enough about the biology around it that often determines whether a treatment will work. This research creates the scientific foundation for bringing that missing layer of biology into view from a standard blood draw.”
“Cancer is not just a collection of malignant cells,” said Vincent A. Miller, MD, Senior Strategic Advisor to LiquidCell Dx and former Chief Medical Officer of Foundation Medicine. “It is also the complex ecosystem around those cells, and that ecosystem can often explain the difference between responses in tumors with otherwise similar genomic features. Making that biology measurable from blood expands what oncologists can know before treatment begins and may inform treatment choice and ultimately patient outcomes. Although initial efforts focused on analysis of data from patients treated with immunotherapies, we see growing evidence that the clinical impact of this work will generalize across many therapeutic classes, therapeutic modalities and tumor types and stages.”
The paper also evaluated established biomarkers directly. In data from patients with a variety of solid tumors with available TMB or PD-L1 data subjected to multivariable analysis, liquid spatial ecotype signals were more significantly associated with overall survival than either TMB or PD-L1.
LiquidCell Dx is focused initially on solid tumors and predicting therapeutic responses across a range of treatment modalities, including immunotherapies, engineered cell therapies (e.g., CAR-T), bispecific antibodies, and antibody-drug conjugates, where there is a lack of biomarkers to guide treatment selection. The paper demonstrated the generalizability of the platform across 17 cancer types, including carcinomas and melanoma, and noted applicability across therapeutic modalities, including immune cell therapies and personalized vaccines. The authors describe spatial ecotypes as fundamental units of tissue biology in multicellular life, with implications for decoding biology in health and disease beyond oncology. The ability to measure such ecosystems from a simple blood draw enables the measurement of spatial biology at an unprecedented scale, unlocking a new layer of biology for clinical discovery and personalized medicine across disease areas.
The paper is titled “Non-invasive profiling of the tumour microenvironment with spatial ecotypes” (DOI: 10.1038/s41586-026-10452-4). Co-first authors are Wubing Zhang, Erin L. Brown, and Abul Usmani. Collaborating institutions include Stanford University, Mayo Clinic, Washington University in St. Louis, Yale University, Columbia University, the Medical College of Wisconsin, the University of Rochester, and the Chan Zuckerberg Biohub San Francisco.
About LiquidCell Dx
LiquidCell Dx is a precision diagnostics company based in San Carlos, California, building a blood-based platform for tumor microenvironment profiling. The company is translating complex tissue biology into blood-based signals for research and clinical development.
For more information, visit liquidcelldx.com.
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