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The immune microenvironment in gastric adenocarcinoma

Nature Reviews Gastroenterology & Hepatology volume 19, pages 451–467 (2022)Cite this article

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Abstract

Like most solid tumours, the microenvironment of epithelial-derived gastric adenocarcinoma (GAC) consists of a variety of stromal cell types, including fibroblasts, and neuronal, endothelial and immune cells. In this article, we review the role of the immune microenvironment in the progression of chronic inflammation to GAC, primarily the immune microenvironment driven by the gram-negative bacterial species Helicobacter pylori. The infection-driven nature of most GACs has renewed awareness of the immune microenvironment and its effect on tumour development and progression. About 75–90% of GACs are associated with prior H. pylori infection and 5–10% with Epstein–Barr virus infection. Although 50% of the world’s population is infected with H. pylori, only 1–3% will progress to GAC, with progression the result of a combination of the H. pylori strain, host susceptibility and composition of the chronic inflammatory response. Other environmental risk factors include exposure to a high-salt diet and nitrates. Genetically, chromosome instability occurs in ~50% of GACs and 21% of GACs are microsatellite instability-high tumours. Here, we review the timeline and pathogenesis of the events triggered by H. pylori that can create an immunosuppressive microenvironment by modulating the host’s innate and adaptive immune responses, and subsequently favour GAC development.

Key points

  • Helicobacter pylori is a major risk factor for gastric adenocarcinoma (GAC).

  • Early detection and eradication of H. pylori are critical for stopping progression from chronic inflammation to GAC.

  • Immune cell populations driving the epithelial transition from normal to metaplasia to dysplasia are largely undefined.

  • As the host’s dampened immune environment can exist for several years prior to GAC, identifying critical inflexion points and associated biomarkers might improve prevention of GAC.

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Fig. 1: Timeline of complications from Helicobacter pylori infection.
Fig. 2: Polymorphonuclear myeloid-derived suppressor cell induction during spasmolytic polypeptide-expressing metaplasia development.
Fig. 3: Differentiation and cell signatures of common immune cells recruited to the stomach in response to Helicobacter pylori infection.

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Acknowledgements

This work was supported by Public Service Grants R01 DK118563 (PI: J.L.M.), 5U19AI11649105 (PIs: A. A. Weiss and J. M. Wells; Project Leader 1: Y.Z.), R01DK083402-10 (PI: Y.Z.) and NCI P30CA023074 and U54CA143924. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The authors also sincerely thank O. Q. Merchant at the University of Michigan for her assistance with the figures.

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    Yana Zavros & Juanita L. Merchant

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Zavros, Y., Merchant, J.L. The immune microenvironment in gastric adenocarcinoma. Nat Rev Gastroenterol Hepatol 19, 451–467 (2022). https://doi.org/10.1038/s41575-022-00591-0

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