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Spatial coupling of microbes and immune cells in solid malignancies.

ABSTRACT: Microbes are an integral component of the tumor microenvironment (TME). However, mechanisms that direct microbial recruitment into tumors and the spatial relationship between intratumoral microbes and host cells remain poorly understood. Here, we show that microbes and immune cells have parallel spatial distribution and that the presence of intratumoral microbes is dependent on T cells. Analysis of human pancreatic ductal adenocarcinomas (PDAC) and lung adenocarcinomas (LUAD) revealed a spatially heterogeneous distribution of lipopolysaccharide (LPS) that is associated with T cell infiltration. Using mouse models of PDAC, we found that microbes were more abundant and diverse in tumors that were enriched in T cells compared to tumors that lacked T cells, despite no significant differences in the fecal microbiome. Consistent with these findings, we detected elevated levels of microbial genes in T cell-enriched tumor nests in human PDAC. Compared to microbe-poor tumor nests, microbe-enriched tumor nests displayed a higher number of myeloid cells, B cells, and plasma cells. Microbe-enriched tumor nests also showed upregulation of immune-related processes, including responses to bacteria, and receptors that mediate mucosal immune responses to microbes. Administration of antibiotics to tumor-bearing mice altered the phenotype and presence of intratumoral myeloid cells and B cells but did not alter T cell infiltration. In contrast, depletion of T cells reduced the presence of intratumoral microbes. Our results identify a novel coupling between microbes and the intratumoral immune landscape, with T cells shaping microbial presence and subsequent microbial-host interactions.

ORGANISM(S): Mus musculus

PROVIDER: GSE213736 | GEO | 2023/12/01

REPOSITORIES: GEO

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