ArticleClinical cancer research : an official journal of the American Association for Cancer Research2022
Multi-omic Characterization of Pancreatic Ductal Adenocarcinoma Relates CXCR4 mRNA Expression Levels to Potential Clinical Targets.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers, 1 of them a synthesis that pooled it.
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Who cites it
16 citing papers in PubMed, 1 synthesis or guideline pooled it, 16 citations in OpenAlex.
- Signaling pathway mechanisms in pancreatic ductal adenocarcinoma tumor microenvironment and emerging targeting strategies for improved prognosis.Oncology reviews · 2026Pooled it
- SIRT6 cooperates with KDM5C to transcriptionally silence MICAL2 and inhibit tumorigenesis in pancreatic cancer.Cell communication and signaling : CCS · 2026Article
- CXCR4 in colorectal cancer: from prognostic marker to immunotherapy guide?BMJ oncology · 2026Article
- CXCR4 mRNA overexpression: an indicator of poor survival and predictor of response to immune checkpoint inhibitors in patients with metastatic colorectal cancer.BMJ oncology · 2026Article
- Review
- CXCR4/CXCL12 axis promotes lymphatic metastasis in tongue squamous cell carcinoma via PI3K/AKT signaling pathway.Journal of translational medicine · 2025Article
- Review
- Tumor-associated macrophages (TAMs): Constructing an immunosuppressive microenvironment bridge for pancreatic ductal adenocarcinoma (PDAC).Cancer pathogenesis and therapy · 2025Review
- Perineural invasion and the "cold" tumor microenvironment in pancreatic cancer: mechanisms of crosstalk and therapeutic opportunities.Frontiers in immunology · 2025Review
- New insights into the role of macrophages in cancer immunotherapy.Frontiers in immunology · 2024Review
- Predicting effect of anti-PD-1/PD-L1 inhibitors therapy for hepatocellular carcinoma by detecting plasma metabolite based on UHPLC-MS.Frontiers in immunology · 2024Article
- CXCR4-modified CAR-T cells suppresses MDSCs recruitment via STAT3/NF-κB/SDF-1α axis to enhance efficacy against pancreatic cancer.Molecular therapy : the journal of the American Society of Gene Therapy · 2023Article
- A chemokine network of T cell exhaustion and metabolic reprogramming in renal cell carcinoma.Frontiers in immunology · 2023Article
- Donor Mesenchymal Stem Cells Program Bone Marrow, Altering Macrophages, and Suppressing Endometriosis in Mice.Stem cells international · 2023Article
- Editorial: Complexity of tumor microenvironment: A major culprit in cancer development.Frontiers in endocrinology · 2022Article
- Editorial: Complexity of tumor microenvironment: A major culprit in cancer development, volume II.Frontiers in endocrinology · 2022Article
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Authors and funding
27 authors at 13 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeChemokines are essential for immune cell trafficking and are considered to have a major impact on the composition of the tumor microenvironment. CX-chemokine receptor 4 (CXCR4) is associated with poor differentiation, metastasis, and prognosis in pancreatic ductal adenocarcinoma (PDAC). This study provides a comprehensive molecular portrait of PDAC according to CXCR4 mRNA expression levels. EXPERIMENTAL
designThe Cancer Genome Atlas database was used to explore molecular and immunologic features associated with CXCR4 mRNA expression in PDAC. A large real-word dataset (n = 3,647) served for validation and further exploratory analyses. Single-cell RNA analyses on a publicly available dataset and in-house multiplex immunofluorescence (mIF) experiments were performed to elaborate cellular localization of CXCR4.
resultsHigh CXCR4 mRNA expression (CXCR4high) was associated with increased infiltration of regulatory T cells, CD8+ T cells, and macrophages, and upregulation of several immune-related genes, including immune checkpoint transcripts (e.g., TIGIT, CD274, PDCD1). Analysis of the validation cohort confirmed the CXCR4-dependent immunologic TME composition in PDAC irrespective of microsatellite instability-high/mismatch repair-deficient or tumor mutational burden. Single-cell RNA analysis and mIF revealed that CXCR4 was mainly expressed by macrophages and T-cell subsets. Clinical relevance of our finding is supported by an improved survival of CXCR4high PDAC.
conclusionsHigh intratumoral CXCR4 mRNA expression is linked to a T cell- and macrophage-rich PDAC phenotype with high expression of inhibitory immune checkpoints. Thus, our findings might serve as a rationale to investigate CXCR4 as a predictive biomarker in patients with PDAC undergoing immune checkpoint inhibition.
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