In luminal gastrointestinal tumors, immune checkpoint inhibitors (ICIs) targeting PD-1, PD-L1 and CTLA-4 have been investigated in multiple settings. The indications for these drugs are primarily dependent on specific biomarkers that imply immunogenicity: overexpression of PD-L1, tumor mutational burden, loss of mismatch repair proteins (dMMR) and/or high microsatellite instability status. Although these markers can be both predictive and prognostic, there is variability in how they are measured and used to guide therapies. Moreover, the use of ICIs can be further refined with a better understanding of the tumor microenvironment and interactions with other available therapies. The purpose of this review is to characterize luminal gastrointestinal tumors' responses to ICIs considering known predictive biomarkers and discuss emerging therapeutic approaches using ICIs.
Keywords: PD-L1; colorectal cancer; esophageal cancer; gastric cancer; immune checkpoint inhibitors; immunotherapy; microsatellite instability; mismatch repair; tumor microenvironment; tumor mutational burden.
Immune checkpoint inhibitors (ICIs) are medications that help the natural immune system fight cancer cells, preventing their growth. In tumors of the gastrointestinal tract, mounting research has shown that ICIs are useful in treatment regimens. However, this depends on certain characteristics of individual cancers, such as how many mutations they have, if they are missing certain enzymes and other considerations. ICIs can also be paired with standard – and nonstandard – treatments like chemotherapy, radiation and other targeted therapy to increase their effectiveness against cancer. This article discusses how ICIs are used in gastrointestinal tract cancers according to the available evidence in the medical literature, and it explores the directions of the research on the forefront of immunotherapy.