GEO series
A platform for multisite immune profiling of premetastatic pancreatic cancer at single cell resolution
GSE300304
Homo sapiens
Other; Expression profiling by high throughput sequencing
30 samples
Submitted 2025/09/02
Platform GPL24676
Summary
Pancreatic ductal adenocarcinoma (PDAC) is characterized by exceedingly high rates of metastatic progression, with the liver representing the most common site of distant spread. Here, we established a platform for multisite immune profiling of human PDAC encompassing the tumor, peripheral circulation, and premetastatic liver, to more comprehensively study how various immune subsets might contribute to patient outcomes. METHODS: Tumor, liver, and blood samples were obtained from patients undergoing resection for non-metastatic PDAC. Derived immune cells underwent paired single-cell RNA and TCR sequencing. Immune composition, cell type functional profiles, and T cell clonal expansion patterns were evaluated across tissue sites. RESULTS: In total, 106,539 immune cells were sequenced, of which 85,748 met criteria for analysis. We identified 32 cell populations, of which seven demonstrated significant enrichment within a particular tissue. Functional profiling revealed tissue-specific differences in cell phenotypes. This included terminally differentiated exhausted CD8 T cells within the tumor, highly active Tregs within the premetastatic liver and tumor, and M1 versus M2 polarization of liver and tumor macrophage populations, respectively. Clonal expansion of T cells was greatest in the liver, which comprised predominantly mature CD8 T cells and MAIT cells. Within the tumor, expanded Treg clones were uniquely abundant, and while expanded clones could be tracked to the blood and premetastatic liver, many of these mapped back to known viral antigens. Leveraging previously validated gene sets, we predicted the tumor reactivity of intratumoral T cells using transcriptional signatures. We demonstrated a high degree of concordance between multiple independent signatures and tracked high-priority TCRs within the blood and liver. CONCLUSION: This study provides a platform, which has already been implemented into ongoing clinical protocols, for immune profiling of human PDAC across the sites most relevant to metastatic progression. Future applications of this work can monitor immune populations throughout metastatic progression to build a temporal database of immune phenotypes and track association with clinical outcomes.
Published in
Kanu EN, Fletcher AA, Bao J et al.
· Cancer immunology, immunotherapy : CII 2025
· PMID 40848148
· doi:10.1007/s00262-025-04146-5
This dataset
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Direct links to NCBI, no account and no request form: the whole study as GSE300304_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 30 samples. Raw sequencing reads are also available from ENA.
Also filed as BioProject PRJNA1277284 and SRA study SRP592338. Searching any of these in the dataset finder brings you back here.
Study design
30 conditions, each sampled once — no replicated groups
Read from 30 sample titles: 30 distinct titles with little repetition. Check it against the sample list below before relying on it.
Samples in this study
0 selected
- GSM9058069 Liver_1_GEX
- GSM9058070 Liver_1_TCR
- GSM9058071 Liver_2_GEX
- GSM9058072 Liver_2_TCR
- GSM9058073 Liver_3_GEX
- GSM9058074 Liver_3_TCR
- GSM9058075 Pancreas_CD45Pos_live_GEX
- GSM9058076 Pancreas_CD45Pos_live_TCR
- GSM9058077 PBMC_GEX
- GSM9058078 PBMC_TCR
- GSM9058079 037_LiverA_GEX
- GSM9058080 037_LiverA_TCR
- GSM9058081 037_LiverB_GEX
- GSM9058082 037_LiverB_TCR
- GSM9058083 037_LiverCcryo_GEX
- GSM9058084 037_LiverCcryo_TCR
- GSM9058085 037_Panc_CD45Pos_GEX
- GSM9058086 037_Panc_CD45Pos_TCR
- GSM9058087 037_PBMC_GEX
- GSM9058088 037_PBMC_TCR
- GSM9058089 036_LiverA_GEX
- GSM9058090 036_LiverA_TCR
- GSM9058091 036_LiverB_GEX
- GSM9058092 036_LiverB_TCR
- GSM9058093 036_LiverC_GEX
- GSM9058094 036_LiverC_TCR
- GSM9058095 036_Panc_CD45Pos_GEX
- GSM9058096 036_Panc_CD45Pos_TCR
- GSM9058097 036_PBMC_GEX
- GSM9058098 036_PBMC_TCR
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