ArticleClinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico2025
The role of the CXCL12/CXCR4 axis in the immunotherapy of non-small cell lung cancer.
Article in Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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Who cites it
4 citing papers in PubMed.
- Relationship between expression of derived factor-1CXC chemokine receptor 4 in tumor tissues of patients with non-small cell lung cancer and postoperative lymph node metastasis.Journal of molecular histology · 2026Article
- G protein-coupled receptors as novel therapeutic targets in non-small-cell lung cancer.Medical review (2021) · 2025Review
- Chemokine Receptors in Peripheral Blood Mononuclear Cells as Predictive Biomarkers for Immunotherapy Efficacy in Non-Small Cell Lung Cancer.Current oncology (Toronto, Ont.) · 2025Review
- C-X-C chemokine receptor family genes in osteosarcoma: expression profiles, regulatory networks, and functional impact on tumor progression.Hereditas · 2025Article
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Funding
Abstract
introductionPeripheral blood mononuclear cells (PBMCs) trafficking is regulated by chemokines, which modulate leukocyte migration toward tumors and may collaborate in the efficacy of immunotherapy. In our study, we investigated whether the CXCL12/CXCR4 axis plays a role in the efficacy of immunotherapy in non-small cell lung cancer (NSCLC) by analyzing CXCR4 expression for CXCR4 in peripheral blood (PB), and the expression of its ligand CXCL12 in tumor.
methodsWe identified PBMCs expressing CXCR4 using flow cytometry in a prospective cohort of NSCLC patients before starting anti-PD-1 immunotherapy. As a control, we studied patients with advanced cancer before starting any non-immunotherapy treatment. The relative frequency of PBMCs was correlated with treatment outcomes. Uni- and multivariate survival analyses were performed. The expression of CXCL12 in tumor tissue was studied and correlated with the expression of its receptor (CXCR4) in PBMCs.
resultsThe experimental group included 39 patients and the control group included 40. Low expression of CXCR4-expressing CD8 + T lymphocytes was correlated with a greater benefit from immunotherapy: median OS NR vs. 22.0 months, HR 0.6, p < 0.01; and median PFS 14.2 vs. 5.0 months, HR 0.38, p = 0.05. These differences were not observed in controls. Low expression in PB of these lymphocytes was correlated with a higher expression of CXCL12 in tumor (trend toward significance: p = 0.14).
conclusionPatients diagnosed with advanced NSCLC with low percentage of cytotoxic T lymphocytes expressing CXCR4 in PB, show greater benefit from immunotherapy, probably due to increased tumor infiltration by lymphocytes in response to CXCL12 produced by the tumor.
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