4.4 Review

Immune evasion mechanisms and therapeutic strategies in gastric cancer

Journal

WORLD JOURNAL OF GASTROINTESTINAL ONCOLOGY
Volume 14, Issue 1, Pages 216-229

Publisher

BAISHIDENG PUBLISHING GROUP INC
DOI: 10.4251/wjgo.v14.i1.216

Keywords

Gastric cancer; Immune evasion; Immune checkpoint; Immunotherapy; Microenvironment

Funding

  1. Natural Science Foundation of China [81672378, 81201521, 81873874, 81773089]
  2. Clinical Research Plan of SHDC [SHDC2020CR2021B]

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This review systematically summarizes the intricate crosstalk between gastric cancer cells and immune cells, and how gastric cancer cells alter immune cells to create an immunosuppressive microenvironment. It also highlights the promising survival advantages of immune checkpoint inhibitor-based immunotherapies in gastric cancer patients.
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.

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