Immune Checkpoint Inhibitors in Gastrointestinal Malignancies

Gastrointestinal malignancies represent a diverse group of diseases, with widely differing etiologies, genomic underpinnings, and therapeutic options. Programmed Death Protein 1 (PD-1) inhibitors have recently been approved for gastroesphageal adenocarcinomas and hepatocellular carcinomas: pembrolizumab and nivolumab, respectively. On the other hand, pancreatic and colorectal adenocarcinomas remain by and large resistant to these treatment modalities, specifically single agent PD-1 blockade. Microsatellite instability has emerged as a strong biomarker of response to PD-1 inhibition in many gastrointestinal malignancies, with the greatest present applicability in colorectal cancer. Multiple additional avenues of research are being pursued, including tests to identify patients who are most likely to respond, as well as strategies to modulate the immune microenvironment for potentiation of immune checkpoint blockade.