C-C chemokine receptor type 7–Interleukin-10–Forkhead box P3 regulatory T-cell axis (CCR7–IL-10–FoxP3 axis)

The CCR7–IL-10–FoxP3 regulatory T-cell axis is a multi-component signaling pathway that regulates the recruitment and immunosuppressive function of regulatory T cells (Tregs). CCR7, a G protein-coupled receptor, mediates the homing of FoxP3-positive Tregs to secondary lymphoid organs and the tumor microenvironment (TME) in response to its ligands, CCL19 and CCL21 [3, 5, 17]. FoxP3 serves as the master transcription factor that defines the Treg lineage and drives the expression of suppressive molecules, including the anti-inflammatory cytokine Interleukin-10 (IL-10) [8, 14]. In various cancers, such as gastric and lung cancer, this axis is upregulated, leading to an accumulation of intratumoral Tregs that suppress cytotoxic CD8+ T-cell activity via IL-10 secretion, thereby promoting tumor evasion and metastasis [6, 12, 18]. Therapeutic strategies targeting this axis involve inhibiting CCR7-mediated migration or modulating IL-10 signaling to restore anti-tumor immunity, though these approaches carry risks of inducing systemic autoimmunity [4, 10]. Drugs such as Pegilodecakin (an IL-10 agonist) and Mogamulizumab (an anti-CCR4 antibody) are used to modulate Treg activity, while experimental CCR7 antagonists are being explored to disrupt Treg homing [4, 9, 14].

Other names

CCR7/IL-10/FoxP3 pathwayTreg homing and suppression axisCCR7-FoxP3-IL10 axis

Modulation of regulatory T-cell recruitment via CCR7, transcriptional control via FoxP3, and effector suppression via IL-10 secretion.