Molecular biology and immunology of gastric cancer peritoneal metastasis

Abstract

Peritoneal metastases occur in 55-60% of patients with gastric cancer (GC) and are associated with a 2% 5-year overall survival rate. There are limited treatment options for these patients, and no targeted therapy or immunotherapy is available. Rational therapeutic targets remain to be found. In this review, we present the published literature and our own recent experience in molecular biology to identify important molecules and signaling pathways as well as cellular immunity involved in the peritoneal metastasis of GC. We also suggest potential novel strategies for improving the outcomes of GC patients with peritoneal metastasis.

Keywords: Gastric cancer (GC); epithelial-mesenchymal transition (EMT); immunology; molecular biology; peritoneal carcinomatosis (PC); peritoneal metastases.

Figure 1

Immunological outline of peritoneal dissemination in GC. DCs, Mφ and NK cells are the innate immune cells directly defend against cancer. DCs and Mφ interact with T cells by further presenting GC antigens to different types of T cells and inducing or disabling immune responses to GC. While GC cells program T cells and M2 Mφ to express immune checkpoint molecules for making effector T cells into exhaustion and modifying Treg to suppress immunity in tumor-infiltrating environments. Immune cells normally secret cytokines to restrict cancer growth. However, the suppressive T cells are unable to produce these cytokines., enhanced peritoneal metastasis in GC;, inhibited peritoneal metastasis in GC. GC, gastric cancer.