Статья

Viral modulation of the CXCL12/CXCR4/CXCR7 axis: mechanisms, impacts on immunity and oncogenesis, and therapeutic opportunities

Usamah SayedFaculty of Allied Medical Sciences, Hourani Center for Applied Scientific Research, Al-Ahliyya Amman University, Amman, Jordan. Electronic address: [email protected]Aya Mohammed DhiaaCollege of Pharmacy, Alnoor University, Nineveh, Iraq. Electronic address: [email protected]Djaloliddin MansurovDepartment of Traumatology, Orthopedics, Neurosurgery and Ophthalmology, Samarkand State Medical University, Samarkand, UzbekistanNorbek KholboyevDepartment of Medicine, Termez University of Economics and Service, Termez, UzbekistanRasim M SalihAl-Zahrawi University College, Karbala, Iraq. Electronic address: [email protected]Mohaned AdilPharmacy college, Al-Farahidi University, Baghdad, Iraq. Electronic address: [email protected]Safa AlkayyatDepartment of Medical Analysis, Medical Laboratory Technique College, The Islamic University, Najaf, Iraq; Centre of Research Impact and Outcome, Chitkara University, Rajpura 140417, Punjab, India. Electronic address: [email protected]

Cancer Treatment and Research Communicationsjournal2026en

ABI

Аннотация

The CXCL12/CXCR4/CXCR7 chemokine axis is a spatial signaling network that links cell positioning to immune function, tissue repair, vascular stability, and niche retention. Under physiological conditions, CXCL12 gradients, receptor bias, receptor crosstalk, and ligand scavenging coordinate leukocyte trafficking, stem/progenitor-cell localization, endothelial integrity, and tissue remodeling. Viruses frequently exploit this system to facilitate entry, dissemination, immune evasion, persistence, and, in some contexts, virus-associated oncogenesis. Across herpesviruses, retro/lentiviruses, hepatotropic viruses, respiratory viruses, HPV, and neurotropic viruses, several recurring strategies emerge: receptor-interface remodeling through heterodimerization, allosteric modulation, or viral GPCR activity; post-translational modification of receptors, including tyrosine sulfation; transcriptional, epigenetic, and miRNA-mediated regulation that sustains CXCL12 production or shifts CXCR4/CXCR7 expression; and redistribution or sequestration of CXCL12 within tissue microenvironments. These mechanisms reshape antiviral immunity by altering leukocyte recruitment, promoting localized inflammation, restricting effector-cell access, and supporting immune-suppressive niches. In virus-associated cancers, CXCL12-axis rewiring contributes to EMT, invasion, angiogenesis, stromal co-option, immune exclusion, and therapy resistance. In this review, we discuss how diverse viruses reprogram the CXCL12-CXCR4-CXCR7/ACKR3 axis at molecular and spatial levels and connect these changes to immune mislocalization, viral persistence, and oncogenic progression. We also evaluate therapeutic opportunities, including CXCR4/CXCR7 antagonists, CXCL12-neutralizing strategies, and biomarker-guided combinations with targeted therapies or immunotherapies. We propose that this axis should be approached not as a uniformly pathogenic pathway, but as a context-dependent spatial system whose therapeutic modulation must be tailored to viral species, tissue compartment, disease stage, and receptor state.

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Темы

Chemokine receptors and signaling Immune cells in cancer Viral-associated cancers and disorders

Идентификаторы

DOI: 10.1016/j.ctarc.2026.101247

Цитирования и источники

Цитирований: 0Использованных источников: 205

Показатели — AkademScholar