The role of the CXCL12/CXCR4 axis in the immunotherapy of non-small cell lung cancer

• Published in: Clinical & translational oncology 2024-12
• Main Authors: Rogado, Jacobo, Pozo, Fernando, Troule, Kevin, Pacheco, María, Adrados, Magdalena, Sánchez-Torres, José Miguel, Al-Shahrour, Fátima, Aspa, Javier, Alfranca, Arantzazu, Romero-Laorden, Nuria, Colomer, Ramon
• Format: Article
• Language: English
• ISSN: 1699-3055; 1699-3055
• DOI: 10.1007/s12094-024-03828-3

Peripheral 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. We 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. The 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