Immune cells may help pancreatic tumors hide from the body’s defenses, with differences between patient groups offering clues that could eventually guide more personalized treatment.
Understanding what makes one pancreatic tumor different from another could help doctors tailor treatment to each patient. Researchers at the University of Cincinnati Cancer Center have found new clues in both cancer cells and the immune cells around them.
The study, recently published in Cancer Research, was led by Nina Steele, PhD, an assistant professor in UC’s College of Medicine and a Cancer Center member, in collaboration with Howard Crawford, PhD, scientific director of the Henry Ford + Michigan State University Pancreatic Cancer Center.
Steele began the project at Henry Ford Health. Working with colleagues there and at UC, she mapped genomic information from a representative sample of Americans diagnosed with pancreatic cancer. The team used a multiomic approach, examining multiple layers of biological information.
“We didn’t have an accurate reflection of all of the patients impacted by the disease reflected in the data,” Steele said. “There had never been a large-scale multiomic effort looking at tens of thousands of biological markers across a diverse cohort of pancreatic cancer patients.”
Immune cells may help cancer hide
Pancreatic cancer incidence and survival vary across American populations, with Black African Americans 20% more likely to develop the disease. Comparing their tumor samples with those from non-African American patients, the researchers found differences in B cells, a type of immune cell. In Black patients’ samples, these cells were more abundant and more immunosuppressive, dampening the body’s natural immune response against cancer.
“This may mean the B cells are helping the cancer cells hide in this patient population,” Steele said. “This could help explain why this population is more likely to get the cancer, and why it’s worse when they get it, but more work is needed on pancreas tissues from individuals that do not have cancer.”
Tumor markers hint at drug resistance
The cancer cells themselves also showed distinct molecular signatures between the two groups.
“The cancer cells make unique RNAs and proteins, so that could be relevant to how individual patients from different groups could respond to targeted therapies like RAS inhibitors,” Steele said. “The markers upregulated in Black patients likely represent a type of cells typically associated with drug resistance, so this biological difference could play a role in outcomes.”
RAS inhibitors target proteins involved in cell growth. Further research is needed to understand the mechanisms behind the observed differences and their effects on outcomes. The findings could eventually help researchers identify new pancreatic cancer subtypes, as has happened in breast and prostate cancer, and develop more personalized treatment approaches.
“The Cancer Center is here to serve everybody, and to find the answers that help all patients,” Steele said. “The hope is to know more about the characteristics of the cancer cells earlier on, so that we have a plan of attack for what therapies come after current standards of care in a very rational way. We’re headed toward forecasting, the ability to better predict what will happen to every patient in their journey before it happens.”
Reference: “Spatial Transcriptomics on a Diverse Pancreatic Cancer Cohort Reveals Race-Related Differences in Tumor Subtypes and Immune Microenvironments” by Yuesong Wu, Daniel James Sålas-Escabillas, Aoqi Xie, Ian M Loveless, Yasmine Baca, Kailee Hartway, Rama Shankar, Samuel D Zwernik, Logan Schneider, Ashley George, Madison George, Allison Wombwell, Julie M Clark, David S Kwon, Bin Chen, Benjamin H Hinrichs, Ralph Francescone, Débora Barbosa Vendramini-Costa, Kerem Ozcan, Zhengfan Xu, Ling Huang, Brian K Theisen, Yuehua Cui, Howard C Crawford and Nina G Steele, 19 October 2026, Cancer research.
DOI: 10.1158/0008-5472.CAN-25-2748
This study was funded by grants from the Lustgarten Foundation and the Sky Foundation and National Cancer Institute grant No. R00CA263154 awarded to Steele.
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