- Fox Chase researchers developed a new tool that helps clinicians understand whether the tissue surrounding a pancreatic tumor is helping fight the cancer or allowing it to grow.
- Using this tool in the lab, the team found that a specialized form of radiation treatment can change the tumor environment to potentially work against the cancer.
- Researchers are now applying this tool to patient samples from a clinical trial to confirm that the same effects are seen in patients treated with this specialized form of radiation and to explore its potential to guide more personalized pancreatic cancer care in the future.
PHILADELPHIA (April 23, 2026) — A new study from researchers at Fox Chase Cancer Center focusing on pancreatic cancer has shown that a new scoring system can provide a single numerical value that reflects whether the tumor microenvironment, the biological “neighborhood” surrounding a tumor, is working to suppress or support that tumor. The results of the laboratory study could ultimately help clinicians improve treatment offered to patients with pancreatic cancer.
The new tool, the Harmonic Output of Stromal Traits Factor (HOST-Factor), is a first-of-its-kind composite scoring system that quantifies the functional state of the tumor microenvironment in pancreatic cancer.
Demonstrating Effectiveness of PLDR Chemoradiation
In the study, Fox Chase researchers used HOST-Factor to demonstrate the effectiveness of pulsed low-dose-rate (PLDR) chemoradiation in the treatment of local pancreatic cells in the vicinity of the cancer cells. Whereas standard chemoradiation pushes these tumor microenvironment cells toward a tumor-promoting state, the HOST-Factor indicated that PLDR chemoradiation stimulated the tumor microenvironment and shifted it toward a tumor-restricting state.
“The HOST-Factor is essentially a way to stage the neighborhood — the microenvironment — rather than just staging the cancer itself,” said senior author Edna “Eti” Cukierman, PhD, Founding Director of the Marvin and Concetta Greenberg Pancreatic Cancer Institute and Co-Leader of the Cancer Signaling and Microenvironment Research Program at Fox Chase.
“In pancreatic cancer, most of the tumor mass is made up of non-cancer material. The HOST-Factor gives us a single, quantitative number to understand whether that neighborhood is working for the patient or against them,” added Cukierman.
She conducted the study with co-lead authors Janusz Franco-Barraza, MD, PhD, an Assistant Research Professor and Manager of the Spatial Immuno-Proteomics Initiative at the Histopathology Facility, and Mariia Dmitrieva, BS, MS, a Research Scientist in the Cukierman Lab, as well as other Fox Chase researchers.
The Challenge of Predicting Disease Behavior
Pancreatic ductal adenocarcinoma (PDAC), which accounts for over 90% of pancreatic cancer cases, possesses a dense, fibrous tumor microenvironment that is largely made up of cancer-associated fibroblasts (CAFs), which are specialized cells that generate a collagenous scaffolding called the extracellular matrix (ECM).
Normally, in the absence of cancer, these type of fibroblastic cells and their natural scaffolding work together as functional units that suppresses tumor growth. But upon cancer onset, many CAFs and their ECM shift into a tumor-supportive state. This shift fuels cancer progression, protects the cancer from treatment, and maintains the immune-suppressed niches, which together create pathways for the growth and spread of the cancer.
For years, researchers have worked to understand which features of this microenvironment predict disease behavior. One major challenge was that no single biological marker, on its own, could reliably predict the various patient-harvested CAF/ECM units’ tumor-suppressiveness or tumor-supportiveness. This is the obstacle Cukierman and her team overcame with the HOST-Factor.
Key Findings
- The HOST-Factor reliably measures changes in the state of the tumor microenvironment. The HOST-Factor integrates various established biological markers of CAF and ECM function into a single composite value that, in this study, detected significant treatment-induced changes that no individual marker could identify on its own.
- PLDR chemoradiation shifts the microenvironment toward an anti-tumor state. In in vitro models, human pancreatic CAF/ECM units treated with PLDR-based chemoradiation generated scaffolds that lost their ability to sustain tumor-promoting fibroblast activation. Results showed an approximately two-fold reduction compared to conventional chemoradiation.
Building Toward Clinical Application
The laboratory findings in this study motivated and support a phase I clinical trial at Fox Chase being led by Joshua Meyer, MD, FASTRO, Director of the Marvin and Concetta Greenberg Pancreatic Cancer Institute, Vice Chair of Translational Research, Professor in the Department of Radiation Oncology, and a coauthor on the HOST-Factor study.
The fully enrolled trial assessed the safety of escalated radiotherapy doses delivered with PLDR to patients with pancreatic cancer that could be treated surgically. The research team is now applying HOST-Factor analysis to pre- and post-treatment patient samples from that study, including as a more comprehensive approach to other tumor microenvironment neighbors besides CAFs, with results to be reported in a future study.
“This paper is chapter one of a larger story,” said Cukierman. “The HOST-Factor lets us ask, ‘Is the microenvironment working for or against our patients? And is our treatment changing that?’ The clinical trial will let us answer those questions and represents a further step in refining the HOST-Factor as a future clinical diagnostic tool in pancreatic as well as numerous other solid cancers.”
The study, “Pulsed Low-Dose-Rate Chemoradiation Induces Stromal Reprogramming in Pancreatic CAF-Generated ECM: Quantification by the HOST-Factor,” was published in Gastro Hep Advances.