Advanced-stage cutaneous T-cell lymphomas (CTCL) are associated with a global decrease in normal T cell numbers and diversity, leading to a profound immunodeficiency and recurrent severe infections. The mechanisms of this normal T-cell depletion remain unclear, although several mechanisms may be suggested. Here we observed that CTCL cell lines and tumor cells from patients with Sezary syndrome expressed Fas ligand mRNA. Fas ligand was not expressed at the cell surface of CTCL cells but was present in the cytoplasm and localized in secretory microvesicles. CTCL cells released extracellular vesicles / exosomes that expressed Fas ligand. Purified exosomes released by CTCL cells induced the apoptosis of Fas-expressing cells in a Fas ligand-dependent manner. These results shed light on a new tumor escape mechanism in Sezary syndrome and contribute to explain the immunodeficiency associated with advanced-stage CTCL.

Cutaneous T-cell lymphoma cells release proapoptotic Fas ligand in lysosomal secretory vesicles