MCW Scientists Identify Patients with Pancreatic Cancer Who May Respond to Immunotherapy

Pancreatic Cancer CellsPancreatic ductal adenocarcinoma (PDAC) has long been notorious for its aggressive nature and genetic complexity, making it difficult for doctors to predict how patients will respond to treatment. In a groundbreaking new study, MCW pancreatic cancer scientists unveiled a promising path forward in the fight against the disease by identifying four distinct subtypes of PDAC based on their tumor microenvironment (TME) immune composition, which describes the types and quantities of immune cells surrounding the tumor. The team discovered that the subtypes with more immune cells showed better outcomes and may respond to personalized treatments like immunotherapy. These novel findings, recently published in Gastroenterology, mark a significant step forward in the understanding of pancreatic cancer biology and open the door to development of cutting-edge precision medicine strategies.

“Using computationally generated gene expression signatures, we identified four unique subtypes of PDAC: immune enriched (IE); immune enriched, fibrotic (IE/F); fibrotic (F); and immune depleted (D). We discovered that IE and IE/F subtypes demonstrated a more favorable prognosis and potential for response to immunotherapy compared with the F and D subtypes,” said Ben George, MD, Professor of Hematology and Oncology, Medical Director of the Center’s Clinical Trials Office (CTO), and the study’s first author. “This novel approach has helped us identify patients who may benefit from immunotherapy, and provides a framework to select patients for prospective clinical trials investigating precision immunotherapy in PDAC.”

“The scientific community has long believed that pancreatic cancer was not responsive to immunotherapy, which uses a person’s own immune system to fight cancer. However, for the first time, our team discovered that pancreatic cancer that spreads to the lungs is biologically distinct, prognostically favorable, and potentially responsive to immunotherapy compared to those that spread to the liver,” said Dr. George.

The research team identified the four PDAC subtypes by studying the gene signatures of patients with pancreatic cancer (1,657) across 14 different datasets, then validating their findings in another patient cohort (79) from the MCW LaBahn Pancreatic Cancer Program. After a deep analysis of the patients’ tumors, they learned that some types of pancreatic cancer have a better outlook and the potential to respond better to immunotherapy—like most lung metastases, which the team classified as subtype IE. Conversely, liver metastases were subtype D, indicating less favorable prognoses.

Scientists have tried developing treatments that target different aspects of the cancer cells, the immune system, and the surrounding tissue. They have also looked closely at the genetic and molecular makeup of PDAC to find new therapeutic options. However, most of these attempts have only worked for a small percentage of patients with specific genetic changes in their cancer cells. Dr. George said results from this study offer a new hope and guidance for personalized treatment strategies, and bring us closer to improved outcomes for patients with the hard-to-treat disease.

“Pancreatic cancer is becoming more common and has a very aggressive clinical course. It’s crucial that we find new ways to treat it,” said Dr. George. “We remain dedicated to this important research, hoping to further characterize the biologically distinct PDAC subtypes and investigate how different treatments can modify the TME of pancreatic cancers. Our goal is to design prospective clinical trials, which will be made available through the MCW Cancer Center, to test various immunomodulatory strategies based on these four subtypes.”

Recognizing the impact of this research, Gastroenterology, the official journal of the American Gastroenterological Association, has dedicated the cover of its May edition to these important findings.

Read the full study in Gastroenterology.