Immune evasion mechanisms and therapeutic strategies in gastric cancer

Abstract

Gastric cancer (GC) is a malignancy with a high incidence and mortality. The tumor immune microenvironment plays an important role in promoting cancer development and supports GC progression. Accumulating evidence shows that GC cells can exert versatile mechanisms to remodel the tumor immune microenvironment and induce immune evasion. In this review, we systematically summarize the intricate crosstalk between GC cells and immune cells, including tumor-associated macrophages, neutrophils, myeloid-derived suppressor cells, natural killer cells, effector T cells, regulatory T cells, and B cells. We focus on how GC cells alter these immune cells to create an immunosuppressive microenvironment that protects GC cells from immune attack. We conclude by compiling the latest progression of immune checkpoint inhibitor-based immunotherapies, both alone and in combination with conventional therapies. Anti-cytotoxic T-lymphocyte-associated protein 4 and anti-programmed cell death protein 1/programmed death-ligand 1 therapy alone does not provide substantial clinical benefit for GC treatment. However, the combination of immune checkpoint inhibitors with chemotherapy or targeted therapy has promising survival advantages in refractory and advanced GC patients. This review provides a comprehensive understanding of the immune evasion mechanisms of GC, and highlights promising immunotherapeutic strategies.

Keywords: Gastric cancer, Immune evasion, Immune checkpoint, Immunotherapy, Microenvironment

Core Tip: Gastric cancer (GC) is one of the most common malignancies with high incidence and mortality. GC can exert versatile mechanisms to induce immune evasion. Here, we systematically summarized the intricate crosstalk among GC cells and various immune cells and mainly focused on how GC cells educate immune cells to create an immunosuppressive microenvironment and facilitate GC cells from attack of the immune system. In addition, we retrieved the latest progression of immune checkpoint inhibitor-based immunotherapies and their combination with conventional therapies. This review provides a comprehensive understanding of the immune evasion mechanism and immunotherapeutic strategies in GC.