Cutaneous Lymphocyte Antigen Is a Potential Therapeutic Target in Cutaneous T-Cell Lymphoma

Cutaneous T-cell lymphoma (CTCL) such as Sézary syndrome or mycosis fungoides corresponds to an abnormal infiltration of T lymphocytes in the skin. CTCL cells have a heterogeneous phenotype and express cell adhesion molecules such as cutaneous lymphocyte antigen (CLA) supporting skin homing. The use of a mAb (HECA-452) against CLA significantly decreased transendothelial migration and survival of CTCL cells from patient samples and My-La cell line. The decrease of CLA expression by inhibition of its maturation enzyme, ST3 β-galactoside α-2,3-sialyltransferase 4, also impaired CTCL cell migration, proliferation, and survival. We confirmed in vivo that treatment with anti-CLA mAb decreased the tumorigenicity as well as dissemination of CTCL cells in different tissues compared with the control group. Our findings provide evidence of the involvement of CLA in CTCL cell migration and survival, supporting that CLA inhibition could represent an actionable therapy in patients with CTCL.