CCR4 in cutaneous T‐cell lymphoma: Therapeutic targeting of a pathogenic driver

New treatments are needed for patients with cutaneous T-cell lymphoma (CTCL), particularly advanced mycosis fungoides (MF) and Sezary syndrome (SS). The immunopathology of MF SS is complex, but recent advances in tumor microenvironment understanding have identified CCR4 as a promising therapeutic target. widely expressed on malignant T cells Tregs the skin peripheral blood SS. interaction its dominant ligands CCL17 CCL22 plays critical role development progression CTCL, facilitating movement into, accumulation of, CCR4-expressing skin, recruiting into microenvironment. Expression upregulated at all stages SS, increasing advancing disease. Several CCR4-targeted therapies being evaluated, including “chemotoxins” targeting via CCL17, CCR4-directed chimeric antigen receptor-modified therapies, small-molecule antagonists, anti-CCR4 monoclonal antibodies. Only one currently approved: mogamulizumab, defucosylated, fully humanized, anti-CCR4, antibody treatment relapsed/refractory Clinical trial da1ta confirm that mogamulizumab an effective well-tolerated or demonstrating clinical value CCR4.