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Review
. 2024 Jun 28;21(7):553-570.
doi: 10.20892/j.issn.2095-3941.2024.0124.

Modeling human gastric cancers in immunocompetent mice

Weihong Zhang  1   2 , Shilong Wang  2 , Hui Zhang  2 , Yan Meng  1 , Shi Jiao  2 , Liwei An  1 , Zhaocai Zhou  2   3
Affiliations
Review

Modeling human gastric cancers in immunocompetent mice

Weihong Zhang et al. Cancer Biol Med. .

Abstract

Gastric cancer (GC) is a major cause of cancer-related mortality worldwide. GC is determined by multiple (epi)genetic and environmental factors; can occur at distinct anatomic positions of the stomach; and displays high heterogeneity, with different cellular origins and diverse histological and molecular features. This heterogeneity has hindered efforts to fully understand the pathology of GC and develop efficient therapeutics. In the past decade, great progress has been made in the study of GC, particularly in molecular subtyping, investigation of the immune microenvironment, and defining the evolutionary path and dynamics. Preclinical mouse models, particularly immunocompetent models that mimic the cellular and molecular features of human GC, in combination with organoid culture and clinical studies, have provided powerful tools for elucidating the molecular and cellular mechanisms underlying GC pathology and immune evasion, and the development of novel therapeutic strategies. Herein, we first briefly introduce current progress and challenges in GC study and subsequently summarize immunocompetent GC mouse models, emphasizing the potential application of genetically engineered mouse models in antitumor immunity and immunotherapy studies.

Keywords: GEMM; Gastric cancer; heterogeneity; immunocompetent; mouse model.

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Conflict of interest statement

No potential conflicts of interest are disclosed.

Figures

Figure 1
Figure 1
Immunocompetent mouse models of GC. (A) Allograft GC models generated by subcutaneous and orthotopic transplantation of mouse gastric cell lines, such as MFC and YTN16, show favorable replicability and stability, but also induce an unnaturally hyperinflammatory response. (B) Chemical carcinogen-induced GC mouse models, such as those using MNU and MNNG, exhibit high mutational burden and immunogenicity. (C) Genetically engineered mouse models of GC generated through genetic manipulation within stomach specific cells have uncovered genotype-phenotype relationships during GC initiation and progression.
Figure 2
Figure 2
Mouse GC models induced by chemical carcinogen administration and/or genetic engineering in immunocompetent mice. Modeling of gastric tumorigenesis by genetic manipulation within distinct cell types has revealed the high heterogeneity in cell origin during human GC initiation. Infection with microorganisms such as H. pylori and S. anginosus accelerates GC tumorigenesis.
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