Dr. Beatty on the Potential for Immunotherapy in GI Malignancies

Gregory L. Beatty, MD, PhD, assistant professor of medicine, director of Tanslation Research, Pancreatic Cancer Research Center, University of Pennsylvania Perelman School of Medicine, discusses the potential for immunotherapy in gastrointestinal (GI) malignancies.

Although there have been signals that immunotherapy can be effective in the treatments of some GI malignancies, challenges persist. Since 70% of the immune system resides in the gut, Beatty says that one of the challenges for the immune system is deciding between staying tolerant or activating. There are a lot of pathogens that are in the gut, so cancers that form in the GI tract have found ways to avoid immune recognition, Beatty explains.

There are subsets of patients who appear to respond to immunotherapy, specifically those who have DNA mismatch repair-deficient cancers. Those tumors have larger numbers of mutations, which alerts the immune system to attack. Checkpoint therapies that target PD-1/PD-L1 have been successful in these tumors. However, the majority of patients with GI malignancies, particularly pancreatic and gastroesophageal cancers, do not respond to immunotherapy, says Beatty.

The next step toward implementing immunotherapy in GI malignancies is conditioning tumors for an immune response, which Beatty says is done through combinations and sequencing.