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

ESDR464 - CCR8 is a new therapeutic target in cutaneous T-cell lymphomas

The scientific meeting of the European Society for Dermatological Research (ESDR) is held yearly, usually in September. With an international attendance of more than 1000 skin scientists from around the globe, the four-day event includes short oral presentations from peer-reviewed abstracts, keynote lectures from international experts, sponsored symposia, satellite programs, educational events as well as an important focus on posters, networking and building collaborations amongst scientists. For more information about this year’s meeting visit our website.