Immunotherapy in Gastrointestinal Malignancies

Gastrointestinal (GI) cancers represent a variety of malignancies, each with a unique interplay between the tumor and local immune microenvironment. The successes that immunotherapy, particularly immune checkpoint inhibition, has brought to various other solid tumors have largely not yielded the same benefits to patients with GI cancers. There are subsets of patients for whom immunotherapy has been FDA approved in recent years. For example, anti-PD-1 therapy is approved for patients with pretreated hepatocellular carcinoma. Additionally, patients with PD-L1-positive gastric cancer are eligible to receive anti-PD-1 therapy in the third line setting. Outside of the rare subset of patients who harbor MSI-H/dMMR tumors, the vast majority of patients with colorectal, anal, biliary tract, and pancreatic cancers have not responded to single-agent immune checkpoint inhibitors. Innovative techniques with thoughtful treatment combinations, adoptive cell therapy, CAR-T cells, as well as novel predictive biomarkers are needed to bring the benefits of immunotherapy to the majority of patients with GI malignancies.