ArticleGastroenterology2024
Intratumoral Cell Neighborhoods Coordinate Outcomes in Pancreatic Ductal Adenocarcinoma.
Article in Gastroenterology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed.
- CD40 agonist mitazalimab with mFOLFIRINOX in untreated metastatic pancreatic cancer: Biomarkers associated with outcomes from OPTIMIZE-1.Cell reports. Medicine · 2025Trial
- Impact of Liver Metastases on Outcomes With Chemotherapy or Immune Checkpoint Inhibitors in Pancreatic Cancer.Immunity, inflammation and disease · 2026Observational
- The spatial architecture of tumor immunity: Emerging predictive biomarkers across cancer.Immunologic research · 2026Review
- Baseline dual-layer spectral CT-based habitat analysis for preoperative prediction of recurrence in pancreatic cancer after radical resection and its association with tumor-stroma ratio.Abdominal radiology (New York) · 2026Article
- Beyond the chaos: How architecture structures tumour biology.The FEBS journal · 2026Review
- Cellular neighborhoods in cancer.Nature cancer · 2026Article
- Nonredundant Immune Checkpoints Direct Therapeutic Resistance to Chemoimmunotherapy in Pancreatic Ductal Adenocarcinoma.Cancer immunology research · 2025Article
- RACK1 attenuates pancreatic tumorigenesis by suppressing acinar-to-ductal metaplasia through inflammatory signaling modulation.Cellular oncology (Dordrecht, Netherlands) · 2025Article
- Multiomics Reveals the Immunologic Features and the Immune Checkpoint Blockade Potential of Colorectal Medullary Carcinoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Article
- Review
- Exogenous or in situ vaccination to trigger clinical responses in pancreatic cancer.Carcinogenesis · 2024Review
- Molecular subtypes and prognostic factors of lung large cell neuroendocrine carcinoma.Translational lung cancer research · 2024Article
- Blockade of IL1β and PD1 with Combination Chemotherapy Reduces Systemic Myeloid Suppression in Metastatic Pancreatic Cancer with Heterogeneous Effects in the Tumor.Cancer immunology research · 2024Article
- Multiplexed Imaging Mass Cytometry Analysis Characterizes the Vascular Niche in Pancreatic Cancer.Cancer research · 2024Article
- Depicting the cellular complexity of pancreatic adenocarcinoma by Imaging Mass Cytometry: focus on cancer-associated fibroblasts.Frontiers in immunology · 2024Article
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19 authors.
Funding
Abstract
BACKGROUND &
aimsPancreatic ductal adenocarcinoma (PDA) is a highly lethal disease characterized by a spatially heterogeneous tumor microenvironment. Within the PDA microenvironment, cells organize into communities where cell fate is influenced by neighboring cells of diverse ontogeny and function. However, it remains unclear how cell neighborhoods in the tumor microenvironment evolve with treatment and impact clinical outcomes.
methodsHere, using automated chromogenic multiplex immunohistochemistry and unsupervised computational image analysis of human PDA tumors, we investigated cell neighborhoods in surgically resected tumors from patients with chemotherapy-naïve PDA (n = 59) and neoadjuvant chemotherapy-treated PDA (n = 57). Single cells were defined by lineage markers (CD3, CD8, Foxp3, CD68, CK19), proliferation (Ki67), and neighboring cells.
resultsDistinct intratumoral immune and tumor cell subsets were defined by neighboring cells. Higher content of stromal-associated macrophages was seen in chemotherapy-naïve tumors from long-term survivors (overall survival >3 years) compared with short-term survivors (overall survival <1 year), whereas immune-excluded tumor cells were higher in short-term survivors. Chemotherapy-treated vs -naïve tumors showed lower content of tumor-associated T cells and macrophages but similar densities of stromal-associated immune cells. However, proliferating tumor cell subsets with immune-rich neighborhoods were higher in chemotherapy-treated tumors. In a blinded analysis of tumors from patients treated with neoadjuvant chemotherapy, a composite index comprising lower quantities of immune-excluded tumor cells and higher spatially distinct immune cell subsets was associated with prolonged survival.
conclusionsTogether, these data provide new insights into discrete cell communities in PDA and show their clinical relevance.
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