ArticleCancer research2022
Quantitative Spatial Profiling of Immune Populations in Pancreatic Ductal Adenocarcinoma Reveals Tumor Microenvironment Heterogeneity and Prognostic Biomarkers.
Article in Cancer research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 57 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
57 citing papers in PubMed.
- Review
- Spatial Configuration of Pancreatic Cancer Is Associated with Disease Recurrence after Neoadjuvant Therapy and Curative-Intent Resection.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026Article
- Spatial omics illuminates tumor heterogeneity.Cell reports methods · 2026Review
- Advances in deciphering intratumoral versus peritumoral heterogeneity of infiltrating lymphocytes in pancreatic cancer: a spatial perspective.Translational oncology · 2026Review
- CD40 Agonism in Pancreatic Ductal Adenocarcinoma: Expression, Biology, and Therapeutic Targeting.Cancers · 2026Review
- Harnessing Cancer Stem Cells and 3D Organoids in Unravelling Spatial and Cellular Heterogeneity in Cancer.International journal of molecular sciences · 2026Review
- High-Dimensional Protein Analysis Uncovers Distinct Immunologic and Stromal Features in Primary and Metastatic Pancreatic Ductal Adenocarcinoma.Cancer research · 2026Article
- Heterocellular crosstalk and architecture of the pancreatic tumour microenvironment.Nature reviews. Cancer · 2026Review
- Intratumoral Three-Cell-Type Clusters Are a Conserved Feature of Endogenous Antitumor Immunity.Cancer immunology research · 2026Article
- Epigenetic and transcriptional control of classical and basal-like cell states in pancreatic ductal adenocarcinoma.Gastroenterology report · 2026Review
- Neoadjuvant therapy-induced remodeling of tumor immune microenvironment in pancreatic ductal adenocarcinoma: a spatial and digital pathology analysis.Virchows Archiv : an international journal of pathology · 2026Article
- Multi-omics Approaches to CCAAT/Enhancer-Binding Protein Beta in Oral Squamous Cell Carcinoma: Crosstalk Between Tumor Cells and Tumor-Associated Macrophages Driving Disease Progression.Current cancer drug targets · 2026Article
- Plectin promotes an aggressive phenotype and represses cytotoxic T cell activity in pancreatic cancer.Frontiers in immunology · 2026Article
- MET Exon 14 Skipping Mutations in Lung Cancer: Clinical-Pathological Characteristics and Immune Microenvironment.Current oncology (Toronto, Ont.) · 2025Article
- Combining Spatial Transcriptomics, Pseudotime, and Machine Learning Enables Discovery of Biomarkers for Prostate Cancer.Cancer research · 2025Article
- Higher density of compact B cell clusters in invasive front may contribute to better prognosis in pancreatic ductal adenocarcinoma.Discover oncology · 2025Article
- Bi-level graph learning unveils prognosis-relevant tumor microenvironment patterns in breast multiplexed digital pathology.Patterns (New York, N.Y.) · 2025Article
- Distinct immune cell infiltration patterns in pancreatic ductal adenocarcinoma (PDAC) exhibit divergent immune cell selection and immunosuppressive mechanisms.Nature communications · 2025Article
- Spatial Architecture of Single-Cell and Vasculature in Tumor Microenvironment Predicts Clinical Outcomes in Triple-Negative Breast Cancer.Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc · 2025Article
- Bioinformatics-based Investigation to Unveiling The miRNA-Immunity Axis in The Tumor Microenvironment of Pancreatic Cancer.F1000Research · 2025Article
Corrections and comments
- Erratum issued
Authors and funding
7 authors.
Funding
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive disease with poor 5-year survival rates, necessitating identification of novel therapeutic targets. Elucidating the biology of the tumor immune microenvironment (TiME) can provide vital insights into mechanisms of tumor progression. In this study, we developed a quantitative image processing platform to analyze sequential multiplexed IHC data from archival PDAC tissue resection specimens. A 27-plex marker panel was employed to simultaneously phenotype cell populations and their functional states, followed by a computational workflow to interrogate the immune contextures of the TiME in search of potential biomarkers. The PDAC TiME reflected a low-immunogenic ecosystem with both high intratumoral and intertumoral heterogeneity. Spatial analysis revealed that the relative distance between IL10+ myelomonocytes, PD-1+ CD4+ T cells, and granzyme B+ CD8+ T cells correlated significantly with survival, from which a spatial proximity signature termed imRS was derived that correlated with PDAC patient survival. Furthermore, spatial enrichment of CD8+ T cells in lymphoid aggregates was also linked to improved survival. Altogether, these findings indicate that the PDAC TiME, generally considered immuno-dormant or immunosuppressive, is a spatially nuanced ecosystem orchestrated by ordered immune hierarchies. This new understanding of spatial complexity may guide novel treatment strategies for PDAC. SIGNIFICANCE: Quantitative image analysis of PDAC specimens reveals intertumoral and intratumoral heterogeneity of immune populations and identifies spatial immune architectures that are significantly associated with disease prognosis.
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