CCR4 as a therapeutic target in cutaneous T-cell lymphomas. (A) Langerhans cells (LC), LAM, and reactive T cells, including Treg cells that suppress reactive T helper and cytotoxic T cells (CTL), are abundant constituents of the tumor microenvironment in MF/SS. Interactions between the chemokines CCL17 and CCL22 and their receptor CCR4 facilitate the intricate crosstalk between a malignant T cell (MF cell) and its microenvironment. (B) Mogamulizumab triggers natural killer (NK) cell-mediated ADCC and depletion of CCR4⁺ MF and Treg cells. (C) Therefore, mogamulizumab may be rationally combined with immunomodulatory agents, both old (eg, interferons) and new (eg, with a monoclonal antibody targeting T-cell costimulatory or coinhibitory receptors), in future therapeutic strategies. IFN-α, interferon-α. Professional illustration by Patrick Lane, ScEYEnce Studios.