ArticleCancer immunology research2025
Combination CXCR4 and PD-1 Blockade Enhances Intratumoral Dendritic Cell Activation and Immune Responses Against Hepatocellular Carcinoma.
Article in Cancer immunology research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed.
- CXCL12 upregulates PD-L1 expression and promotes M2 polarisation of tumour-associated macrophages to confer anti-PD-1 resistance in gastric cancer.Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association · 2026Article
- Article
- Targeting cytokine/chemokine signaling to convert immunologically cold tumors into hot: Emerging strategies in cancer immunotherapy.Acta pharmaceutica Sinica. B · 2026Review
- Dual Specificity Phosphatase 4 Enhances Immunotherapy Response by Inhibiting TGF-β1 Secretion in Hepatocellular Carcinoma.Cancers · 2026Article
- Overcoming CXCR4-Mediated T-Cell Exclusion Potentiates Antitumor Cytotoxicity in Fibrolamellar Carcinoma.Gastroenterology · 2026Article
- Overcoming MDSC-Mediated Immunosuppression in Hepatocellular Carcinoma: From Mechanisms to Novel Immunotherapeutic Approaches.Cancers · 2026Review
- CXCR4: A Promising Novel Strategy for Lung Cancer Treatment.Biomolecules · 2026Review
- PRDM1 Drives a TIM3+ Macrophage Immunosuppressive Niche via LGALS9 Signaling in Prostate Cancer Progression.Oncology research · 2026Article
- Nanosystem-Mediated Intercellular Crosstalk Modulation in the Tumor Microenvironment for Enhanced Cancer Immunotherapy.Drug design, development and therapy · 2026Review
- CXCR4-Targeted Nanotherapeutics: A Promising Approach for Liver Fibrosis and Hepatocellular Carcinoma Management.International journal of nanomedicine · 2026Review
- Metabolic dysfunction and GZMKFrontiers in immunology · 2026Review
- 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
- Inhibiting B cells enhances the efficacy of STING agonism or immune checkpoint blockade in hepatocellular carcinoma.Nature communications · 2025Article
- Immune microenvironment in hepatocellular carcinoma: from pathogenesis to immunotherapy.Cellular & molecular immunology · 2025Review
- Combination immunotherapy in hepatocellular carcinoma: synergies among immune checkpoints, TKIs, and chemotherapy.Journal of hematology & oncology · 2025Review
- Machine learning-driven multi-omics analysis identifies a prognostic gene signature associated with programmed cell death and metabolism in hepatocellular carcinoma.Biological procedures online · 2025Article
- Application of Immune Checkpoint Inhibitors in Cancer.MedComm · 2025Review
- Rewriting the dendritic cell code in cancer-from subset identity to immunotherapeutic design.FEBS letters · 2025Review
- Chemokines: Orchestration of the Tumor Microenvironment and Control of Hepatocellular Carcinoma Progression.Cancer medicine · 2025Review
- New insights into combined immunotherapy for hepatocellular carcinoma associated with liver cirrhosis.Frontiers in immunology · 2025Review
Corrections and comments
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Authors and funding
10 authors.
Funding
Abstract
Immune checkpoint inhibitors have revolutionized the treatment of unresectable hepatocellular carcinoma (HCC), but their impressive efficacy is seen in just a fraction of patients. One key mechanism of immunotherapy resistance is the paucity of dendritic cells (DC) in liver malignancies. In this study, we tested combination blockade of PD-1 and CXCR4, a receptor for CXCL12, a pleiotropic factor that mediates immunosuppression in tumors. Using orthotopic grafted and autochthonous HCC models with underlying liver damage, we evaluated treatment feasibility and efficacy. In addition, we examined the effects of treatment using immunofluorescence, flow cytometric analysis of DCs in vivo and in vitro, and RNA sequencing. The combination anti-CXCR4 and anti-PD-1 therapy was safe and significantly inhibited tumor growth and prolonged survival in all murine preclinical models of HCC tested. The combination treatment successfully reprogrammed antigen-presenting cells, revealing the potential role of conventional type 1 DCs (cDC1) in the HCC microenvironment. Moreover, DC reprogramming enhanced anticancer immunity by facilitating CD8+ T-cell accumulation and activation in the HCC tissue. The effectiveness of anti-CXCR4/PD-1 therapy was compromised entirely in Batf3 knockout mice deficient in cDC1s. Thus, combined CXCR4/PD-1 blockade can reprogram intratumoral cDC1s and holds the potential to potentiate antitumor immune response against HCC.
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Registered trials
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