The bioactive content of cutaneous T-cell lymphoma cell line-derived exosomes

Cutaneous T- Cells Lymphoma (CTCL) is defined as a non-Hodgkin lymphoma, representing a heterogeneous group of T cell lymphoma. Cancer-derived exosomes are nano-sized vesicles released by cancer cells that serve as vehicles for the transfer of biologic materials to recipient cells. They contain mainly oncoproteins, oncogenes, chemokine receptors, transcripts of proteins, and miRNAs to modulate the host microenvironment to support immune escape, tumor growth, progression, chemo-resistance and metastasis. However, data on CTCL are strikingly absent.

The aims of the study were to detect exosomes in CTCL cell lines, to characterize their proteins and microRNAs content, their uptake into recipient cells, and to explore their functional role.

Exosomes were isolated from several CTCL cell lines by differential ultracentrifugation. Their morphology was confirmed by electron microscopy, and their size and concentration were analyzed using a nanoparticle tracking system. The exosomes were profiled for microRNAs content by Affymetrix microarray and for proteins content by proteomics mass spectrometry. Specific cytokines, immune modulators, and microRNAs known to reprogram the tumor microenvironment and to induce tumor progression were found in CTCL-derived exosomes. Exosomes derived from migrated leukemic CTCL cell line were internalized into indolent skin CTCL cell line, deliver their exosomal microRNAs, protect them from death induced by doxorubicn, and enhance their migration.

This study provides the first evidence of a role of exosomes in CTCL. Our findings point to a novel mechanism whereby CTCL cells communicate within the tumor heterogeneity cells and microenvironment to promote cancer.