Immune landscape in pancreatic cancer

Pancreas cancers just have not been sensitive to immune therapy, and those of us in the field are trying to sort out is why that is, what makes this cancer so different," says Marina Pasca di Magliano, Ph.D. What has been lacking is even a basic understanding of the variety and individual differences in immune response between patients."

The new research lays a foundation for future translational studies and clinical trials, with the ultimate goal of one day being able to use personalized molecular profiles to determine which immunotherapies would be of greatest benefit to each patient.

Years in the making, the study represents the effort of nearly 40 U-M clinicians and bench scientists working closely together to develop a trove of data that research groups in the field can draw upon for years to come, the team says.

Along with single-cell analysis, the group employed high-definition multiplex immunofluorescence and mass cytometry which combines mass spectrometry and flow cytometry to evaluate the complex biology of tumor samples in multiple ways.

Early in their cancer journey, however, most patients have a tissue sample collected via needle biopsy so that doctors can obtain a definitive diagnosis so Carpenter coordinated the collection of research samples at the same time.

Blood samples were also collected from patients, allowing researchers to examine changes to immune cells circulating in the blood and correlate them with what was happening in a patient's tumor microenvironment, adds co-first author Samantha Kemp, a graduate student studying molecular and cellular pathology.

"I think there is often a surprising disconnect between research labs and clinics, even in something as straightforward as bio-specimen collection," Carpenter notes. Along with the clinical and laboratory efforts, data analysis was critical to the study, Pasca di Magliano stresses. Those efforts were led by Steel, Kemp and Veerin Sirihorachai, a graduate student in cancer biology.

"With single-cell sequencing especially, the actual acquisition of the data is relatively straightforward, but then analyzing the data is incredibly complex," Pasca di Magliano says.

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