T-regulatory cell chemokine receptors (Treg chemokine receptors)

T-regulatory cell (Treg) chemokine receptors are a specialized group of G protein-coupled receptors (GPCRs) that govern the migration and localization of immunosuppressive T cells. Prominent members include CCR4 and CCR8, which are highly expressed on Tregs and respond to chemokines such as CCL17, CCL22, and CCL1 produced within the tumor microenvironment (TME) (Frontiers in Immunology, 2019). By facilitating the infiltration of Tregs into tumors, these receptors play a critical role in establishing an immunosuppressive milieu that allows cancer cells to evade the host immune system (Cancer Letters, 2016). Therapeutic interventions targeting these receptors, such as the CCR4-targeting antibody mogamulizumab or emerging CCR8 antagonists, aim to reduce Treg-mediated suppression and enhance the efficacy of other immunotherapies like checkpoint inhibitors (Nature, 2021). However, because Tregs are vital for maintaining self-tolerance, pharmacological modulation of these receptors poses a significant risk of inducing systemic autoimmune reactions and inflammatory toxicities (Journal of Clinical Investigation, 2020). Clinical monitoring for skin rashes and colitis is often required for patients receiving drugs targeting these receptors (FDA Label: Mogamulizumab).

Other names

Regulatory T cell chemokine receptorsTreg-associated chemokine receptorsTreg-homing receptors

Antibody-dependent cellular cytotoxicity (ADCC) to deplete Treg cells or competitive antagonism to block Treg recruitment into tissues.