CCL20-CCR6 signaling in tumor microenvironment: Functional roles, mechanisms, and immunotherapy targeting

Abstract

Chemokine CC motif ligand 20 (CCL20) is a molecule with immunomodulatory properties that is involved in the regulation of diseases such as chronic inflammation, autoimmune diseases, and cancer. It operates by binding to its specific receptor, CC chemokine receptor type 6 (CCR6), and activating a complex intracellular signaling network. Building on its established role in inflammatory diseases, recent research has expanded our understanding of CCL20 to encompass its critical contributions to the tumor microenvironment (TME), highlighting its significance in cancer progression. Numerous studies have emphasized its prominent role in regulating immune responses. Consequently, Monoclonal antibodies against CCL20 and inhibitors of CCR6 have been successfully developed to block downstream signaling, making the CCL20-CCR6 axis a promising and critical target in the TME. This offers potential immunotherapeutic strategies for cancers. In this review, we summarize the biological consequences of CCL20-CCR6 mediated signaling, its role and mechanisms in the TME, and its potential applications. We suggest that the CCL20-CCR6 axis may be a novel biomarker for tumor diagnosis and prognosis, as well as a therapeutic target in various cancers.