Chemokine receptors on T-regulatory cells

Chemokine receptors on T-regulatory (Treg) cells are a group of G protein-coupled receptors (GPCRs) that mediate the migration, recruitment, and retention of immunosuppressive Tregs within tissues, particularly the tumor microenvironment (TME) [1, 2]. Key members of this group include CCR4 and CCR8, which are highly and selectively expressed on tumor-infiltrating Tregs compared to peripheral T cells [4, 9]. These receptors respond to specific chemokine ligands, such as CCL22 and CCL17 for CCR4, and CCL1 for CCR8, which are often secreted by tumor cells and myeloid cells to facilitate the accumulation of Tregs that suppress anti-tumor immune responses [2, 7]. In oncology, these receptors are targeted to selectively deplete intratumoral Tregs or block their recruitment, thereby enhancing the activity of effector T cells and improving the efficacy of immune checkpoint inhibitors [3, 12]. Therapeutic agents include monoclonal antibodies like mogamulizumab, which targets CCR4, and various clinical-stage candidates targeting CCR8, many of which are designed to induce antibody-dependent cellular cytotoxicity (ADCC) [1, 11]. Beyond cancer, these receptors play critical roles in maintaining immune tolerance and are involved in the pathogenesis of inflammatory and autoimmune conditions [5, 8].

Other names

Treg chemokine receptorsCCR4CCR8CCR5CCR6CXCR3CCR10

Depletion of regulatory T cells via antibody-dependent cellular cytotoxicity (ADCC) and inhibition of Treg recruitment to the tumor microenvironment by blocking chemokine-mediated chemotaxis [1, 12].