C–C motif glycoprotein ligand 5 (CCL5) and its GPCR CCR5: Macromolecular game-changers in cancer biology

T cells is augmented, hence fortifying anticancer immunity. Data from several tumors reveal both detrimental and beneficial effects, dependent on the tumor microenvironment (TME) and therapeutic context. Translational techniques employing CCR5 antagonists such as Maraviroc, GAG-binding modulators, glycoengineered CCL5 variants, delivery systems, and their integration with immune checkpoint inhibitors (ICIs) and targeted therapies are highlighted for their considerable therapeutic promise. Critical research priorities, encompassing single-cell phenotyping, CRISPR-mediated screening of chemokine pathways, and structural-functional mapping, are outlined to facilitate precise modulation of the CCL5/CCR5 axis in targeted cancer therapy. This review addresses structural biology and tumor immunology to identify the CCL5/CCR5 axis as a multifaceted yet promising biological target for innovative cancer therapeutics.