Mapping pancreatic cancer to improve immunotherapy

Gregory L. Beatty, an associate professor of hematology-oncology and member of Penn Medicine’s Abramson Cancer Center, and his team focus on improving immunotherapy for pancreatic cancer.

Training the body’s own immune system to attack cancer cells is known as immunotherapy and it’s a treatment option that’s been highly effective for many cancer types, including lung cancer and melanoma. However, despite decades of research, immunotherapy has yet to break through for some of the most challenging types of cancer, including pancreatic cancer, which has a five-year survival rate of about 10%.

Gregory Beatty holds up a lab sample in a lab coat.
Gregory L. Beatty is an associate professor of hematology-oncology and member of Penn Medicine’s Abramson Cancer Center. (Image: Courtesy of Penn Medicine News)

Researchers use the phrase “tumor microenvironment” to refer to the many different types of cells that exist side by side within a tumor, and it’s a big reason why the current immunotherapy approaches have had limited success in certain cancer types.

Gregory L. Beatty, an associate professor of hematology-oncology and member of Penn Medicine’s Abramson Cancer Center, and his team are focused on improving immunotherapy for pancreatic cancer. They’re using an innovative approach to repurpose an old technology to map the tumor microenvironment and find better ways for immunotherapy drugs to navigate the landscape.

Beatty explains what the tumor microenvironment is, and its role in pancreatic cancer treatment and research. “Inside the tumor, we find cancer cells, along with microbes, blood vessels, fibroblasts, and many different types of immune cells, including T cells, B cells, myeloid cells, macrophages, and more. The way that these cells are distributed throughout the tumor can vary from person to person, even if they have the same type of cancer. It’s like each tumor is a unique city with different neighborhoods of cells,” he says. “Our goal is to find how and why the cells are grouped in different ways and to figure out their effects on the immune response to cancer so that we can develop strategies to make immunotherapy work better for patients, particularly those who have very few effective treatment options.”

Beatty’s team recently published two studies using this IHC technique: In Cell Reports Medicine, they looked at the different neighborhoods of cells within the pancreatic cancer tumor microenvironment to better understand how the different cells influence each other. “With our IHC technique, we found that T cells drive the presence of microbes in tumors, which then recruit other immune cells, like B cells and myeloid cells, to establish a microenvironment that is more vulnerable to attack by the immune system. This finding confirmed the importance of T cells as master orchestrators of tumor destruction and emphasized the importance of finding ways to improve the penetration of T cells into tumors,” Beatty says.

In another study in Gastroenterology, the team, led by Max Miller Wattenberg, used the same technique to look at biopsies taken from patients with pancreatic cancer enrolled in a clinical trial and who had received chemotherapy before surgery. “We found that we could predict which patients’ cancers would respond favorably to chemotherapy based on the immune cell neighborhoods and their proximity to the cancer cell neighborhoods within the tumor microenvironment,” Beatty says.

Read more at Penn Medicine News.