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Series GSE213736 Query DataSets for GSE213736
Status Public on Dec 01, 2023
Title Spatial coupling of microbes and immune cells in solid malignancies.
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary 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.
 
Overall design RNA isolated from T cell-poor ("cold") tumors and T cell-enriched ("hot") tumors treated with or without anti-CD4 and CD8 antibodies or antibiotics were analyzed using QuantSeq 3' mRNA sequencing.
 
Contributor(s) Li Y, Chang RB, Lee JW, Beatty GL
Citation(s) 38307029
Submission date Sep 19, 2022
Last update date Mar 01, 2024
Contact name Gregory L. Beatty
E-mail(s) gregory.beatty@pennmedicine.upenn.edu
Phone (215) 746-7764
Organization name University of Pennsylvania
Department Medicine
Street address 3400 Civic Center Blvd, South Pavilion, Rm 8-107
City Philadelphia
State/province PA
ZIP/Postal code 19104
Country USA
 
Platforms (1)
GPL19057 Illumina NextSeq 500 (Mus musculus)
Samples (16)
GSM6592930 Cold tumor, no treatment, sample 1
GSM6592931 Cold tumor, no treatment, sample 2
GSM6592932 Cold tumor, no treatment, sample 3
Relations
BioProject PRJNA882182

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Supplementary file Size Download File type/resource
GSE213736_Tumors_treatment.tpm.txt.gz 1.2 Mb (ftp)(http) TXT
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Raw data are available in SRA
Processed data are available on Series record

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