Application of immune checkpoint inhibitors and microsatellite instability in gastric cancer

Abstract

In this editorial we comment on the article by Li published in the recent issue of the World Journal of Gastroenterology. We focus specifically on the application of immune checkpoint inhibitors (ICIs) and microsatellite instability (MSI) in gastric cancer (GC). The four pillars of GC management have long been considered, including surgery, chemotherapy, radiotherapy and targeted therapy. However, immunotherapy has recently emerged as a ”fifth pillar”, and its use is rapidly expanding. There are four principal strategies for tumor immunotherapy: ICIs, tumor vaccines, adoptive immunotherapy and nonspecific immunomodulators. Of them, ICIs are the most advanced and widespread type of cancer immunotherapy for GC. Recent breakthrough results for ICIs have paved the way to a new era of cancer immunotherapy. In particular, inhibition of the PD-1/PD-L1 axis with ICIs, including nivolumab and pembrolizumab, has emerged as a novel treatment strategy for advanced GC. Unfortunately, these therapies are sometimes associated with often subtle, potentially fatal immune-related adverse events (irAEs), including dermatitis, diarrhea, colitis, endocrinopathy, hepatotoxicity, neuropathy and pneumonitis. We must be aware of these irAEs and improve the detection of these processes to prevent inappropriate discharges, emergency department revisits, and downstream complications. Recent studies have revealed that MSI-high or mismatch- repair-deficient tumors, regardless of their primary site, have a promising response to ICIs. So, it is important to detect MSI before applying ICIs for treatment of GC.

Keywords: Gastric cancer, Immune checkpoint inhibitors, Microsatellite instability, Immunotherapy, Immune-related adverse events

Core Tip: The immune checkpoint proteins including PD-1/PD-L1, cytotoxic T-lymphocyte antigen-4 play significant roles in the field of cancer immunotherapy. As a result, monoclonal antibodies block these immune checkpoint proteins have been utilized broadly in patients with gastric cancer (GC). However, the treatment-emergent adverse events of autoimmune-like toxicities in patients treated with immune-related immune checkpoint inhibitors (ICIs) have also been observed. These may be related to microsatellite instability (MSI). So, it is important to detect MSI before applying ICIs for treatment of GC.