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Evolution of immune and stromal cell states and ecotypes during gastric adenocarcinoma progression

ABSTRACT: Understanding how the tumor microenvironment (TME) is orchestrated along the continuum of gastric adenocarcinoma (GAC) may uncover novel therapeutic strategies. Here, we performed comprehensive single-cell profiling of precancerous lesions, localized and metastatic GACs, identifying alterations in TME cell states and phenotypes during tumorigenesis and progression. IgA+ plasma cells appear to be the most active regulators in the premalignant microenvironment, whereas immunosuppressive myeloid and stromal subsets dominated the late-stage GACs. We discover six TME ecotypes, four of which are unique to the premalignant/progression in the continuum, with two ecotypes, identified in primary GACs, showing strong associations with histopathologic, genomic characteristics and prognosis. Extensive stromal remodeling is evident with GAC progression. High SDC2 expression in cancer-associated fibroblasts (CAFs) correlates with aggressive phenotypes and poor survival and SDC2 overexpression in CAFs contributes to tumor growth. This study illustrates a roadmap of the GAC TME and highlights potential targets for further investigation.

ORGANISM(S): Homo sapiens

PROVIDER: GSE234129 | GEO | 2023/06/10

REPOSITORIES: GEO

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