Emerging Roles of C-C Motif Ligand 11 (CCL11) in Cancers and Liver Diseases: Mechanisms and Therapeutic Implications

Abstract

C-C motif ligand 11 (CCL11) is a multifunctional chemokine that regulates immunity, angiogenesis, and tissue remodeling. In addition to its allergic inflammation role, CCL11 exhibits context-dependent dual functions in relation to cancer progression. In liver diseases, it mediates injury, fibrosis, and inflammation while serving as a disease biomarker. This review systematically examines CCL11-receptor interactions and their immunomodulatory mechanisms in cancers and hepatic pathologies. We highlight CCL11's therapeutic potential as both a prognostic marker and immunotherapeutic target. By integrating molecular and clinical insights, this work advances the understanding of CCL11's pathophysiological roles and facilitates targeted therapy development.

Keywords: cancer; chemokine CCL11; inflammation; liver disease; therapeutic target.

Figure 1

Schematic representation of CCL11 signaling mechanisms in immune regulation and disease pathogenesis. This illustration comprehensively outlines the pleiotropic functions of CCL11 in orchestrating immune cell recruitment, activation, and disease progression. Through interactions with its cognate receptors (CCR2, CCR3, and CCR5), CCL11 modulates diverse cellular responses in both immune and stromal compartments. In oncological contexts, CCL11 demonstrates dual functionality, facilitating tumor progression via immune escape mechanisms while simultaneously exhibiting tumor-suppressive properties. These effects are mediated through regulating the proliferation, differentiation, and biology of Treg, macrophage, TAM, DC, and MDSC. Furthermore, CCL11 critically regulates eosinophil and basophil biology in both inflammatory and neoplastic conditions. Beyond immune modulation, CCL11 exerts significant effects on endothelial and epithelial cell functions, while upregulating matrix metalloproteinases (MMP-2 and MMP-3) to effect angiogenesis and extracellular matrix remodeling. Red arrows represent promotion, and blue arrows represent inhibition. The figure was created by BioRender online software (BioRender.com accessed on 30 March 2025).