A new map of the immune environment for pancreatic cancer may guide immunotherapy-ScienceDaily

A new study, led by the University of Michigan’s Rogel Cancer Center, combines single-cell RNA sequencing with two other research techniques to create the most robust and detailed portrait of a network of interactions that suppress the immune response in the body. created. Around the pancreatic tumor.

Team survey results displayed in the journal Nature CancerIt puts a new spotlight on the fact that the immune response varies greatly from patient to patient and from tumor to tumor. This needs to be taken into account when new immunotherapeutic combinations for fatal diseases are developed.

“Pancreatic cancer wasn’t sensitive to immunotherapy. That’s why we’re trying to solve it in this area,” says Marina, senior author of the study. Dr. Pasca di Magriano said. , Professor of Surgery and Cellular and Developmental Biology in Michigan Medicine. “What is lacking is even a basic understanding of the diversity of immune responses between patients and individual differences.”

The new study lays the foundation for future translational studies and clinical trials, with the ultimate goal being to use personalized molecular profiles to determine the immunotherapy that will maximize the benefit to each patient. That is.

According to the team, the study has been in close collaboration with nearly 40 UM clinicians and bench scientists over the years, a pile of data that will be available to research groups in the field for years to come. Represents an effort to develop.

In addition to single-cell analysis, this group employs high-resolution multiplex immunofluorescence and mass spectrometry (combining mass spectrometry and flow cytometry) to perform complex biology of tumor samples in multiple ways. I evaluated it with.

“I think an important lesson for me as a clinician is that making immunotherapy work in this disease remains difficult due to the complexity we are just beginning to understand.” Said Philip Bedner, MD, co-lead author of the study. , Associate Professor of Surgery. “This task opens the door to understanding these intricacies and how they can be overcome.”

One of the key findings of this study was a new potential biomarker that appeared in the bloodstream of a subset of patients with pancreatic cancer. It is an immunoreceptor called TIGIT (T cell immunoreceptor with Ig and ITIM domains).

“When people talk about immunotherapy, they’re mainly talking about targeting a few specific molecules, PD-1 and CTLA4,” said co-author, a professor of molecular and integrated physiology. Says Dr. Howard Crawford. Internal medicine. “These research efforts show that it’s not just the two villains who block the immune system and contribute to the ineffectiveness of immunotherapy. TIGIT didn’t really bother me.”

Importantly, researchers found that the expression of TIGIT in a patient’s blood closely corresponds to its activity in tumors.

“Therefore, it suggests that there may be a non-invasive method of analyzing individual patients to see if they are candidates for future treatment targeting that particular checkpoint receptor. This will be a significant step forward for current standard treatments, “says Nina. Dr. Steele, a postdoctoral fellow in Pasca di Magriano’s lab and one of the first four authors of the study.

Another unique aspect of the study was the width and depth of the samples collected, the researchers point out.

Unusually, the analysis included a significant number of samples from patients with advanced pancreatic cancer. Only about 1 in 4 patients with pancreatic cancer are candidates for surgery, and patients with early-stage illness rely on samples collected during surgery, which is very common in many studies. And co-lead author Eileen Carpenter, MD, Ph.D. , Fellow of Gastroenterology.

However, early in the cancer journey, most patients collect tissue samples by needle biopsy so that doctors can get a definitive diagnosis. Therefore, Carpenter also coordinated the collection of research samples.

Blood samples are also collected from patients, allowing researchers to examine changes in immune cells that circulate in the blood and correlate them with what is happening in the patient’s tumor microenvironment, co-lead author Samantha Kemp. Is a graduate student studying molecular and cytopathology.

“I think there are often surprising disconnects between laboratories and clinics, even as simple as collecting biological samples,” Carpenter said. “I think the bridge we built and the contributions of so many different labs speak to the University of Michigan’s collaborative environment. There’s a reason we were able to accomplish this task here.”

In addition to clinical and laboratory efforts, Pasca di Magliano emphasizes that data analysis is important for research. These efforts were led by Steel, Kemp, and Veerin Sirihorachai, a graduate student in cancer biology.

“The actual acquisition of data is relatively easy, especially with single-cell sequencing, but the analysis of the data is very complex,” says Pasca di Magliano.

Single-cell analysis loses spatial information about cells. Therefore, the group led by co-lead author Timothy Frankel, an assistant professor of surgery, MD also used a technique called multiple immunohistochemistry. This allows you to identify multiple cell types within tissue slides while maintaining relative tumor cell location. For components in micro environments.