Chemokines and cancer: new immune checkpoints for cancer therapy

The current review focuses on two chemokine-chemokine receptor interactions: CXCL10-CXCR3 and CCL1-CCR8. We show that CXCL10 acts on CD4+ and CD8+ T cells to enhance anti-tumor immunity, and explore the translational perspectives of these findings. As for CCR8 very recently, we identified a novel subset of CCR8+CD4+FOXp3+ regulatory T cells (Treg) that are major drivers of immune regulation. We observed that one of the four CCR8 ligands, CCL1, produced by these cells, potentiates their suppressive activity via induction of CCR8, FOXp3, CD39, Granzyme-B, and IL-10 in a positive feedback mechanism, making them master drivers of immune regulation. Collectively, this suggests blocking the CCR8-CCL1 interaction, alone or combined with other immune checkpoint inhibitors, as an approach to treat malignant diseases.