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Review
. 2022 Sep 8;14(18):4378.
doi: 10.3390/cancers14184378.

Incorporating Immunotherapy in the Management of Gastric Cancer: Molecular and Clinical Implications

Alessandro Agnarelli  1 , Viviana Vella  1 , Mark Samuels  1 , Panagiotis Papanastasopoulos  1 , Georgios Giamas  1
Affiliations
Review

Incorporating Immunotherapy in the Management of Gastric Cancer: Molecular and Clinical Implications

Alessandro Agnarelli et al. Cancers (Basel). .

Abstract

Gastric cancer has a median survival of 11 months, and this poor prognosis has not improved over the last 30 years. Recent pre-clinical data suggest that there is high tumour-related neoantigen expression in gastric cancer cells, suggesting that a clinical strategy that enhances the host's immune system against cancer cells may be a successful approach to improve clinical outcomes. Additionally, there has been an increasing amount of translational evidence highlighting the relevance of PD-L1 expression in gastric cancer cells, indicating that PD-1/PD-L1 inhibitors may be useful. Several molecular subgroups of gastric cancer have been identified to respond with excellent outcomes to immunotherapy, including microsatellite instable tumours, tumours bearing a high tumour mutational burden, and tumours related to a chronic EBV infection. In gastric cancer, immunotherapy has produced durable responses in chemo-refractory patients; however, most recently there has been a lot of enthusiasm as several large-scale clinical trials highlight the improved survival noted from the incorporation of immunotherapy in the first line setting for advanced gastric cancer. Our review aims to discuss current pre-clinical and clinical data supporting the innovative role of immunotherapy in gastric cancer.

Keywords: EBV; H. pylori; PD-L1; gastric cancer; immune microenvironment; immunotherapy.

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Conflict of interest statement

Georgios Giamas is editor of Cancer Gene Therapy and founder/chief scientific officer of Stingray Bio. No other conflict are declared.

Figures

Figure 1
Figure 1
Main features of GC subtypes. Schematic representation of the molecular characteristics associated with GC molecular subtypes.
Figure 2
Figure 2
H. pylori and EBV mechanisms of infection at a glance. H. pylori infection causes a local inflammation state with consequent infiltration of inflammatory cells, and increased risk of gastric carcinogenesis (left panel), EBV infection process, associated with development of EBV-associated GC (right panel).
Figure 3
Figure 3
PD-L1 on tumour cells works through the PD-1 receptor on T cells to induce immune cell inactivation. Treatment with immune checkpoint inhibitors inhibits this interaction, often through monoclonal antibodies against PD-1 and PD-L1, restoring immune cell function against tumour cells.
See this image and copyright information in PMC

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