Novel Blood Test Reveals Key Tumor Microenvironment Signals Predictive of Immunotherapy Outcomes in Sarcoma
Aqtual, Inc., a precision medicine company focused on developing advanced cell-free DNA (cfDNA) diagnostics for oncology and chronic diseases, has announced new research findings demonstrating the capabilities of its active chromatin cfDNA platform to simultaneously evaluate multiple dimensions of cancer biology from a single blood sample. The results suggest that the technology may offer a powerful, noninvasive method for monitoring the tumor microenvironment, assessing treatment response, and identifying emerging resistance mechanisms in cancer patients.
The findings, generated through a collaboration with investigators at the renowned Princess Margaret Cancer Centre, were published in the peer-reviewed journal npj Precision Oncology and are being further expanded through new analyses presented at the 2026 Annual Meeting of the American Society of Clinical Oncology in Chicago.
According to the company, the research demonstrates that active chromatin profiling can simultaneously capture immune-related, stromal, and tumor-derived biological signals using a single blood-based assay. This multi-dimensional approach may provide clinicians and researchers with a more comprehensive understanding of how cancers respond to therapy and evolve over time, particularly in diseases where obtaining repeated tissue biopsies is difficult or impractical.
Expanding the Scope of Liquid Biopsy Technologies
Liquid biopsy technologies have become increasingly important in modern oncology because they provide a less invasive alternative to traditional tissue biopsies. By analyzing tumor-derived material circulating in the bloodstream, physicians can obtain valuable information about a patient’s cancer without requiring surgical procedures or repeated tissue sampling.
Most currently available liquid biopsy platforms focus primarily on identifying tumor-specific genetic mutations, methylation patterns, or circulating tumor DNA (ctDNA) levels. While these approaches have proven valuable, they often provide only a partial picture of the biological processes driving cancer progression and treatment response.
Aqtual’s active chromatin cfDNA platform seeks to go beyond conventional mutation-based testing by analyzing active chromatin signatures present within circulating DNA fragments. These signatures can reveal information about gene regulation and transcriptional activity occurring within tumors and surrounding tissues.
As a result, the technology is designed to capture not only tumor-specific genomic information but also signals originating from immune cells and stromal components within the tumor microenvironment.
This broader perspective may allow clinicians to better understand the complex biological interactions that influence cancer growth, treatment response, and resistance development.
Study Focused on Advanced Leiomyosarcoma
The published study evaluated a cohort of 30 patients with advanced leiomyosarcoma who were treated with a durvalumab-based combination immunotherapy regimen.
Leiomyosarcoma is a rare and aggressive soft tissue sarcoma that originates from smooth muscle cells. Patients with advanced disease often face limited treatment options, and predicting which individuals are most likely to benefit from immunotherapy remains a significant challenge.
Researchers analyzed baseline plasma samples using Aqtual’s active chromatin cfDNA platform and investigated whether specific biological signatures detected in blood were associated with clinical outcomes.
The results identified multiple categories of signals that correlated with patient responses and progression-free survival.
Importantly, all of these signals were derived from a single blood sample, highlighting the platform’s ability to simultaneously assess several distinct aspects of tumor biology.
Immune Signatures Associated With Improved Outcomes
One of the most significant findings involved immune-related biological programs detected in patient plasma samples.
Researchers identified signatures associated with B-cell activation and T-cell activation that were linked to improved progression-free survival among patients receiving immunotherapy.
These immune-associated programs appeared to reflect a more favorable immunological environment and may help identify patients who are more likely to respond to checkpoint inhibitor-based treatment strategies.
Because immunotherapy effectiveness often depends on the ability of a patient’s immune system to recognize and attack cancer cells, the identification of blood-based immune biomarkers could provide valuable guidance when selecting treatment approaches.
The findings suggest that active chromatin cfDNA profiling may offer a noninvasive way to evaluate immune readiness before treatment begins.
Stromal Remodeling Signals Linked to Resistance
In addition to immune-related findings, the study revealed that stromal remodeling signatures were associated with poorer clinical outcomes.
Specifically, researchers observed that biological programs related to extracellular matrix organization correlated with treatment resistance and shorter progression-free survival.
The tumor stroma consists of supportive cells, connective tissue, blood vessels, and extracellular matrix components that surround cancer cells. Increasing evidence suggests that stromal biology plays a critical role in shaping the tumor microenvironment and influencing therapeutic response.
Excessive stromal remodeling can create physical and biological barriers that limit immune cell infiltration and reduce the effectiveness of anticancer therapies.
The ability to detect stromal activity through a blood test provides an additional layer of biological insight that is generally unavailable through conventional liquid biopsy technologies.
These findings highlight the importance of evaluating not only tumor-specific alterations but also the surrounding microenvironment that contributes to treatment resistance.
Tumor Genomic Features Also Predicted Clinical Outcomes
Beyond immune and stromal biology, the platform also captured tumor-associated genomic features that correlated with patient outcomes.
Researchers identified associations between clinical benefit and measures such as copy number variation and tumor fraction.
Patients with tumor fractions exceeding a specific threshold showed differences in progression-free survival outcomes, suggesting that circulating tumor-derived genomic signals continue to provide valuable prognostic information alongside immune and stromal biomarkers.
The ability to integrate these genomic features into a broader biological framework is one of the distinguishing characteristics of Aqtual’s platform.
Rather than evaluating tumor genetics in isolation, the technology aims to provide a more complete picture of cancer biology by combining genomic, immune, and microenvironmental information within a single assay.
Strong Correlation With Tumor Tissue Biology
An important aspect of the study involved comparing plasma-derived active chromatin signals with traditional tumor tissue analyses.
Researchers found that promoter activity measured in blood demonstrated strong agreement with matched tumor RNA sequencing data. The correlation coefficient reached 0.81, indicating a high degree of consistency between blood-based measurements and tissue-derived transcriptional activity.
This finding suggests that the biological signals captured through circulating DNA closely reflect the same underlying gene expression programs occurring within the tumor itself.
Such concordance is particularly significant because it supports the potential use of blood-based testing as a surrogate for more invasive tissue analyses.
If validated in larger studies, this capability could help reduce reliance on repeat biopsies while still providing clinically meaningful biological information.
New ASCO Analysis Explores Resistance Evolution
Building upon the published findings, investigators presented additional research at the 2026 ASCO Annual Meeting examining how biological signals change over time as tumors adapt to therapy.
The new analysis utilized paired baseline and progression samples collected from the same patients, allowing researchers to monitor dynamic changes in immune, stromal, and tumor-associated genomic features during treatment.
Particular attention was given to patients who initially experienced clinical benefit but later developed disease progression.
By examining longitudinal changes in blood-based biomarkers, investigators sought to gain a deeper understanding of the biological mechanisms that drive acquired resistance.
These analyses provide an early glimpse into resistance biology in a setting where repeated tissue biopsies are often difficult, risky, or simply not feasible.
The ability to monitor resistance evolution through blood samples could eventually support more adaptive treatment strategies and earlier therapeutic intervention.
Addressing Challenges in Leiomyosarcoma
Leiomyosarcoma presents unique challenges for liquid biopsy research.
Unlike many other cancers, leiomyosarcoma typically exhibits a relatively low tumor mutation burden. This characteristic can limit the effectiveness of conventional ctDNA approaches that depend heavily on detecting tumor-specific mutations.
Additionally, obtaining tissue biopsies from patients with advanced sarcoma can be technically difficult due to tumor location, patient health status, or procedural risks.
These limitations create a need for alternative methods capable of generating meaningful biological information without relying exclusively on mutation detection.
Active chromatin profiling may offer a solution by capturing broader biological signals related to gene regulation, immune activity, and stromal remodeling while still supporting traditional genomic analyses such as copy-number profiling.
A New Framework for Liquid Biopsy
According to Aqtual leadership, the significance of the findings extends beyond any individual biomarker identified in the study.
Dr. Diana Abdueva, Co-Founder and Chief Executive Officer of Aqtual, emphasized that the true innovation lies in the platform’s architecture and ability to simultaneously analyze multiple dimensions of cancer biology from a single library preparation.
Traditional liquid biopsy technologies typically focus on one category of information, such as mutations, tissue origin, or DNA fragmentation patterns. In contrast, Aqtual’s platform aims to integrate immune state, stromal state, and tumor genomic information into a unified analysis.
This approach may be particularly valuable in sarcoma and other cancers where conventional ctDNA methods often face technical limitations and repeat tissue biopsies are rarely practical.
While the current findings are encouraging, researchers caution that the study involved a relatively small cohort of patients and requires validation in larger independent populations.
Additional studies are already underway to further evaluate the platform’s predictive capabilities, assess its performance across multiple cancer types, and determine its potential role in guiding treatment decisions.
Nevertheless, the results represent an important step forward in the evolution of liquid biopsy technologies. By simultaneously capturing immune, stromal, and tumor-associated biology from a single blood sample, Aqtual’s active chromatin cfDNA platform may offer a new way to monitor treatment response, understand resistance mechanisms, and personalize cancer care.
As oncology increasingly moves toward precision medicine approaches, technologies capable of providing comprehensive and dynamic insights into tumor biology may become critical tools for clinicians seeking to optimize treatment strategies and improve patient outcomes.
About Aqtual, Inc.
Aqtual, Inc. is a precision medicine company developing products for chronic disease management and oncology utilizing a novel cell-free DNA-based platform. Aqtual’s proprietary platform evaluates protein regulation, epigenetics, and transcriptomics solely using cell-free DNA fragments found in the blood. The platform yields efficient and robust real-time analysis of disease and treatment while overcoming the limitations of previous cell-free DNA methodologies.
