ArticleCell communication and signaling : CCS2024
VDR promotes pancreatic cancer progression in vivo by activating CCL20-mediated M2 polarization of tumor associated macrophage.
Article in Cell communication and signaling : CCS, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers, 1 of them a synthesis that pooled it.
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Who cites it
15 citing papers in PubMed, 1 synthesis or guideline pooled it, 19 citations in OpenAlex.
- Vitamin D and Pancreatic Ductal Adenocarcinoma-A Review of a Complicated Relationship.Nutrients · 2024Pooled it
- CCL20-CCR6 axis in autoimmune disease and cancer progression: clinical and therapeutic implications.Cell communication and signaling : CCS · 2026Review
- Vitamin D receptor signaling in inflammatory senescence-associated skin aging: Mechanisms and therapeutic potentials.Journal of cell communication and signaling · 2026Article
- Tumor cell intrinsic mechanisms of immune escape.Cell communication and signaling : CCS · 2026Review
- Integrating multi-omics and machine learning to uncover CCL20 as a potential regulator of the immunosuppressive microenvironment in lung adenocarcinoma.Frontiers in immunology · 2026Article
- Tumor Microenvironment-Responsive Nanoparticles for Pancreatic Cancer Imaging and Treatment.International journal of nanomedicine · 2026Review
- The value of lipid metabolism-related genes in pancreatic cancer immunotherapy and drug prediction.Journal of gastrointestinal oncology · 2025Article
- Vitamin D Protects Pancreatic Cancer (PC) Cells from Death and DNA Damage Induced by Oxidative Stress.Antioxidants (Basel, Switzerland) · 2025Article
- Enhanced homing and efficacy of HER2-CAR T cells via CXCR5/CCR6 co-expression for HER2-positive NSCLC.Journal of translational medicine · 2025Article
- CCL20 in the tumor microenvironment: implications for cancer progression and therapeutic approaches.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2025Review
- USP15 Facilitates Colorectal Cancer Immune Evasion through SMYD3/CCL2-Dependent Myeloid-Derived Suppressor Cell Recruitment.Cancer immunology research · 2025Article
- Unveiling the mechanisms of CEBPD-orchestrated TAM polarization through RGS2/PAR2 pathway and its impact on ICB efficacy in clear cell renal cell carcinoma.Journal for immunotherapy of cancer · 2025Article
- A novel prognostic model for lung squamous cell carcinoma based on multi-omics analysis and machine learning.PloS one · 2025Article
- Suramin blocked hCAP18/LL-37-induced macrophage recruitment and M2 polarization to enhance the therapeutic efficacy of 1,25(OH)Frontiers in nutrition · 2025Article
- Analysis of Pancreatic Cancer Genetic Risk Factors in a Multi-Ethnic Population Sample.World journal of oncology · 2024Article
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Authors and funding
16 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundActivation of VDR pathway was a promising anti-tumor therapy strategy. However, numerous clinical studies have demonstrated the effect of activating VDR is limited, which indicates that VDR plays a complex role in vivos.
methodsWe analyzed the TCGA database to examine the association between VDR expression and immune cell infiltration in pancreatic adenocarcinoma (PAAD). Western blot, ELISA, ChIP, and dual-luciferase reporter assays were performed to determine the mechanism of VDR regulating CCL20. Migration assay and immunofluorescence were used to investigate the role of CCL20 in M2 macrophage polarization and recruitment. We employed multiplexed immunohistochemical staining and mouse models to validate the correlation of VDR on macrophages infiltration in PAAD. Flow cytometry analysis of M2/M1 ratio in subcutaneous graft tumors.
resultsVDR is extensively expressed in PAAD, and patients with elevated VDR levels exhibited a significantly reduced overall survival. VDR expression in PAAD tissues was associated with increased M2 macrophages infiltration. PAAD cells overexpressing VDR promote macrophages polarization towards M2 phenotype and recruitment in vitro and vivo. Mechanistically, VDR binds to the CCL20 promoter and up-regulates its transcription. The effects of polarization and recruitment on macrophages can be rescued by blocking CCL20. Finally, the relationship between VDR and M2 macrophages infiltration was evaluated using clinical cohort and subcutaneous graft tumors. A positive correlation was demonstrated between VDR/CCL20/CD163 in PAAD tissues and mouse models.
conclusionHigh expression of VDR in PAAD promotes M2 macrophage polarization and recruitment through the secretion of CCL20, which activates tumor progression. This finding suggests that the combination of anti-macrophage therapy may improve the efficacy of VDR activation therapy in PAAD.
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