ArticleProceedings of the National Academy of Sciences of the United States of America2020
CXCR4 inhibition in human pancreatic and colorectal cancers induces an integrated immune response.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 169 papers.
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169 citing papers in PubMed, 247 citations in OpenAlex.
- Motixafortide, cemiplimab, gemcitabine and nab-paclitaxel in metastatic pancreatic cancer: a single-arm phase 2 study with single-cell correlatives.Nature communications · 2026Trial
- A phase 2 trial of CXCR4 antagonism and PD1 inhibition in metastatic pancreatic adenocarcinoma reveals recruitment of T cells but also immunosuppressive macrophages.Oncoimmunology · 2025Trial
- Colitis-associated colorectal carcinogenesis: molecular mechanisms and therapeutic potential.Molecular biomedicine · 2026Review
- Secreted protein circuits in the gastrointestinal tumour microenvironment: determinants of immunotherapy response and resistance.Journal of translational medicine · 2026Review
- Immunohistochemical analysis and scRNA-Seq identifies vascular endothelial CXCR4 expression as a predictor of poor prognosis in pancreatic ductal adenocarcinoma.Translational oncology · 2026Article
- Migration of immune cells in tumors and inflammation: molecular mechanisms and therapeutic targets.Signal transduction and targeted therapy · 2026Review
- Interpretable and scalable spatial gene set activity analysis with GESSO uncovers functional tissue architecture.bioRxiv : the preprint server for biology · 2026Article
- Lysine lactylation-mediated post-translational modification: Molecular mechanisms and therapeutic target exploration in tumour drug resistance.Clinical and translational medicine · 2026Review
- AMD3100 modulates the secretome responses of human Mesenchymal Stromal Cells but not their inhibitory effect on T cell proliferation.Scientific reports · 2026Article
- Association of CXCR7 and CXCR4 expression with tumor immune phenotypes in tubo-ovarian high-grade serous carcinoma.Irish journal of medical science · 2026Article
- C-X-C chemokine receptor type 4 (CXCR4) antagonism in precision oncology: Clinical applications and future directions.Cancer pathogenesis and therapy · 2026Review
- Identification of tolerogenic dendritic cells-related prognostic biomarkers in Wilms tumor via machine learning integration.Discover oncology · 2026Article
- Multi-Omics reveals SPP1 + malignant and CXCR4Discover oncology · 2026Article
- Chemokine-chemokine receptor axis: Emerging immunotherapeutic paradigms for solid tumor microenvironment reprogramming.Chinese medical journal · 2026Review
- Review
- Overcoming CXCR4-Mediated T-Cell Exclusion Potentiates Antitumor Cytotoxicity in Fibrolamellar Carcinoma.Gastroenterology · 2026Article
- Spatial and functional polarization of cancer-associated fibroblasts with CXCR4-mediated immune modulation in hepatocellular carcinoma.Hepatology communications · 2026Article
- Integrated single-cell and spatial transcriptomic analysis reveals mCAF-SPP1⁺ macrophage-T cell crosstalk shaping immunosuppressive niches in colorectal cancer liver metastasis.Journal of translational medicine · 2026Article
- Peritumoural adipose tissue drives immune evasion in colorectal cancer via adipose-mesenchymal transformation.Nature cell biology · 2026Article
- Immunosuppressive tumor microenvironment shape pancreatic cancer unresponsive to current immunotherapies.World journal of clinical oncology · 2026Review
109 more citing papers are in PubMed but not listed here.
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Authors and funding
26 authors at 6 institutions in 3 countries.
Funding
Abstract
Inhibition of the chemokine receptor CXCR4 in combination with blockade of the PD-1/PD-L1 T cell checkpoint induces T cell infiltration and anticancer responses in murine and human pancreatic cancer. Here we elucidate the mechanism by which CXCR4 inhibition affects the tumor immune microenvironment. In human immune cell-based chemotaxis assays, we find that CXCL12-stimulated CXCR4 inhibits the directed migration mediated by CXCR1, CXCR3, CXCR5, CXCR6, and CCR2, respectively, chemokine receptors expressed by all of the immune cell types that participate in an integrated immune response. Inhibiting CXCR4 in an experimental cancer medicine study by 1-wk continuous infusion of the small-molecule inhibitor AMD3100 (plerixafor) induces an integrated immune response that is detected by transcriptional analysis of paired biopsies of metastases from patients with microsatellite stable colorectal and pancreatic cancer. This integrated immune response occurs in three other examples of immune-mediated damage to noninfected tissues: Rejecting renal allografts, melanomas clinically responding to anti-PD1 antibody therapy, and microsatellite instable colorectal cancers. Thus, signaling by CXCR4 causes immune suppression in human pancreatic ductal adenocarcinoma and colorectal cancer by impairing the function of the chemokine receptors that mediate the intratumoral accumulation of immune cells.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.