Study reveals secrets of ‘hot’ and ‘cold’ pancreatic cancer tumors

So-called “hot” tumors filled with T cells are often considered to be more sensitive to immunotherapy compared to “cold” tumors with fewer T cells, but a clear demonstration of why has eluded cancer biologists—until now. A team from Penn Medicine’s Abramson Cancer Center (ACC) discovered that whether a tumor is hot or cold is determined by information embedded in the cancer cells themselves. In a new study published this week in Immunity, researchers probe the role of “tumor heterogeneity,” cancer cells’ ability to move, replicate, metastasize, and respond to treatment. These new findings could help oncologists more precisely tailor treatments to a patient’s unique tumor composition.

T cell low tumor

Recent studies from Penn Medicine and other institutions have suggested that the degree to which T cells are attracted to a tumor is regulated by genes specific to that tumor. “There is no disputing that targeting immune cells has led to promising outcomes for many cancer patients, but not every person responds to these types of treatments,” said senior author Ben Stanger, a professor of gastroenterology and cell and developmental biology in the Perelman School of Medicine. “Every tumor is different, so we’re investigating how to use the underlying biology of tumor cells to successfully treat more cancer patients.” Stanger is also director of the Pancreatic Cancer Research Center.

Pancreatic cancer is predicted to become the second leading cause of cancer death in the United States by 2025.

Pancreatic tumors span the spectrum of T cell infiltration, but the basis for this heterogeneity is poorly understood. In this study, the Penn team created a library of pancreatic tumor cell lines from a mouse model of pancreatic adenocarcinoma. These cell lines, when implanted in normal mice with a working immune system, grew into tumors that fell into the hot and cold categories, with cold tumors being the dominant type. In addition, they found that whether a tumor was hot or cold determined whether it would respond to immunotherapy.

Read more at Penn Medicine News.