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Series GSE162791 Query DataSets for GSE162791
Status Public on Nov 27, 2023
Title BTLA+CD200+ B cells dictate the divergent immune landscape and immunotherapeutic resistance in metastatic vs. primary pancreatic cancer
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary Response to cancer immunotherapy in primary versus metastatic disease has not been well-studied. We found primary pancreatic ductal adenocarcinoma (PDA) is responsive to diverse immunotherapies whereas liver metastases are resistant. We discovered divergent immune landscapes in each compartment. Compared to primary tumor, liver metastases in both mice and humans are infiltrated by highly anergic T cells and MHCII-lo IL10+ macrophages that are unable to present tumor-antigen. Moreover, a distinctive population of CD24 + CD44 – CD40 – B cells dominate liver metastases. These B cells are recruited to the metastatic milieu by Muc1 hi IL18 hi tumor cells, which are enriched >10-fold in liver metastases. Recruited B cells drive macrophage-mediated adaptive immune-tolerance via CD200 and BTLA. Depleting B cells or targeting CD200/BTLA enhanced macrophage and T-cell immunogenicity and enabled immunotherapeutic efficacy of liver metastases. Our data detail the mechanistic underpinnings for compartment-specific immunotherapy responsiveness and suggest that primary PDA models are poor surrogates for evaluating immunity in advanced disease.
Overall design For RNA-Seq experiments, mouse pancreatic primary tumors and liver metastatic tumors were harvested 3 weeks after orthotopic implantation and processed for bulk RNA-Seq. Alternatively, for single cell RNA-seq, CD45+ leukocytes were FACS-sorted from mouse pancreatic primary tumors or liver metastatic tumors 3 weeks after orthotopic implantation, and processed for 10X droplet-based single cell RNA-seq.
Web link
Contributor(s) Leinwand JC, Diskin B
Citation(s) 35948648
Submission date Dec 07, 2020
Last update date Nov 28, 2023
Contact name Joshua Caleb Leinwand
Organization name Columbia University Irving Medical Center
Department Surgery
Street address 177 Fort Washington Ave, 7th Floor
City New York
State/province NY
ZIP/Postal code 10032
Country USA
Platforms (1)
GPL21103 Illumina HiSeq 4000 (Mus musculus)
Samples (8)
GSM4959959 Primary tumor - bulk RNA seq rep_1
GSM4959960 Primary tumor - bulk RNA seq rep_2
GSM4959961 Primary tumor - bulk RNA seq rep_3
BioProject PRJNA683026
SRA SRP296802

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Supplementary file Size Download File type/resource
GSE162791_RAW.tar 376.6 Mb (http)(custom) TAR (of MTX, TSV)
GSE162791_counts.fpkm.csv.gz 440.8 Kb (ftp)(http) CSV
GSE162791_counts.normalized.csv.gz 539.7 Kb (ftp)(http) CSV
GSE162791_counts.raw.csv.gz 404.3 Kb (ftp)(http) CSV
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Raw data are available in SRA
Processed data are available on Series record
Processed data provided as supplementary file

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