464 CCR8 is a new therapeutic target in cutaneous T-cell lymphomas

Cutaneous T-cell lymphomas (CTCL) are rare non-Hodgkin of skin-tropic T cells. Advanced-stage CTCL frequently refractory to treatment and early relapses common. There is a clear unmet need for new treatments with long-term efficacy in CTCL. CCR8 chemokine receptor expressed by skin resident memory cells which suspected be the tumor origin mycosis fungoides. also strongly tumor-infiltrating Treg involved immune escape. We combined blood flow cytometry 13 patients healthy controls, vitro stimulation cells, Nanostring gene expression analysis, single cell RNA sequencing analysis on human study function was overexpressed as compared controls’ CD4 engagement its ligands CCL18 CCL1 induced significant Erk1/2 phosphorylation. together IL-2 higher Sezary proliferation alone. Expression ligand mRNA were associated shorter progression-free survival. Finally, confirmed CCL8 CCL18, 2 ligands, such keratinocytes macrophages. These data support use anti-CCR8 depleting monoclonal antibodies treatment.