ArticleCancer research2011
CXCL12/CXCR4 blockade induces multimodal antitumor effects that prolong survival in an immunocompetent mouse model of ovarian cancer.
Article in Cancer research, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 146 papers.
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Who cites it
146 citing papers in PubMed.
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- Selected Chemokines as Prognostic Biomarkers and Therapeutic Targets in Ovarian Cancer.Current issues in molecular biology · 2026Review
- Regulatory T cells in cancer and inflammation.Signal transduction and targeted therapy · 2026Review
- The Treg-cell death axis in lung cancer: implications for immune evasion and novel therapeutic strategies.Molecular cancer · 2026Review
- Discovery of Novel 2-Morpholine Tetrahydroisoquinoline CXCR4 Antagonists with Unique Properties.Journal of medicinal chemistry · 2026Article
- Mapping CSC-Mediated Ovarian Cancer Chemoresistance via CXCR4-PET to Guide Precision Cisplatin Re-Sensitization Therapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- G-CSF promotes H3K27ac-modified KLF5 to activate CXCR4 expression and drive colon cancer growth and metastasis.European journal of medical research · 2026Article
- Study on the regulation of Treg cell infiltration by EZH2 through CXCR4/CXCL12 in diffuse large B-cell lymphoma.Clinical and experimental medicine · 2025Article
- Chemokine Receptors in Peripheral Blood Mononuclear Cells as Predictive Biomarkers for Immunotherapy Efficacy in Non-Small Cell Lung Cancer.Current oncology (Toronto, Ont.) · 2025Review
- Regulatory T cells in the tumour microenvironment.Nature reviews. Cancer · 2025Review
- Article
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- Cancer immune evasion, immunoediting and intratumour heterogeneity.Nature reviews. Immunology · 2025Review
- CD4Science advances · 2025Article
- Uncovering a new mechanism of ischemic stroke: a study of the association between γδ T cells and immunoinflammation.Frontiers in immunology · 2025Review
- Neutrophil diversity and function in health and disease.Signal transduction and targeted therapy · 2024Review
- Chemokines Signature and T Cell Dynamics in Leishmaniasis: Molecular insight and therapeutic application.Expert reviews in molecular medicine · 2024Review
- CXCL12-loaded-hydrogel (CLG): A new device for metastatic circulating tumor cells (CTCs) capturing and characterization.Heliyon · 2024Article
- Targeting cytokine and chemokine signaling pathways for cancer therapy.Signal transduction and targeted therapy · 2024Review
86 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
17 authors.
Funding
Abstract
The chemokine CXCL12 and its receptor CXCR4 are expressed widely in human cancers, including ovarian cancer, in which they are associated with disease progression at the levels of tumor cell proliferation, invasion, and angiogenesis. Here, we used an immunocompetent mouse model of intraperitoneal papillary epithelial ovarian cancer to show that modulation of the CXCL12/CXCR4 axis in ovarian cancer has multimodal effects on tumor pathogenesis associated with induction of antitumor immunity. siRNA-mediated knockdown of CXCL12 in BR5-1 cells that constitutively express CXCL12 and CXCR4 reduced cell proliferation in vitro, and tumor growth in vivo. Similarly, treatment of BR5-1-derived tumors with AMD3100, a selective CXCR4 antagonist, resulted in increased tumor apoptosis and necrosis, reduction in intraperitoneal dissemination, and selective reduction of intratumoral FoxP3(+) regulatory T cells (Treg). Compared with controls, CXCR4 blockade greatly increased T-cell-mediated antitumor immune responses, conferring a significant survival advantage to AMD3100-treated mice. In addition, the selective effect of CXCR4 antagonism on intratumoral Tregs was associated with both higher CXCR4 expression and increased chemotactic responses to CXCL12, a finding that was also confirmed in a melanoma model. Together, our findings reinforce the concept of a critical role for the CXCL12/CXCR4 axis in ovarian cancer pathogenesis, and they offer a definitive preclinical validation of CXCR4 as a therapeutic target in this disease.
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