Exosomes are small extracellular vesicles that contain proteins, lipids, and nucleic acids. They aid in cell-cell communication, influence local and distant microenvironments and may play a role in cancer development. 

Exosomes contain a significant number of microRNAs (miRNAs), which operate as essential post-transcriptional regulators of gene expression. Emerging evidence suggests that dysregulated miRNA expression disrupts tumor immunity and plays a critical role in the development of several cancers, including cutaneous T-cell lymphoma (CTCL). While research into the involvement of exosomes in the most common CTCL, mycosis fungoides (MF), is still in its early stages, several miRNAs have already captured the attention of researchers as intriguing candidates for much-needed diagnostic and prognostic indicators, as well as novel treatment targets. 

In an experiment, the presence of tumor-derived exosomes in MF was tracked using transmission electron microscopy and nanoparticle tracking analyses. 

The results confirmed the existence of MF-derived exosomes for the first time. In addition, miR-1246 emerged as a prominent miRNA in the MF cell line exosomal content and the role of miR-155 in the pathogenesis of MF was validated. 

miR-155 overexpression is one of the most studied and is linked to enhanced malignancy proliferation and tumor cell survival.  The findings of this study added to the evidence for miR-155s general role in MF, including its ability to increase cell migration of malignant MF cells.  Both miR-155 and miR-1246 are found in the exosomes of MF cell lines. ExomiR-1246 expression was significantly increased in the plasma of 18 patients with advanced MF, presenting clinically with plaque and tumor skin lesions, but not in the plasma of healthy persons. 

In terms of total circulating cell-free miRNA (cfmiRNA), plasma levels of both cfmiR-155 and cfmiR-1246 were higher in patients with advanced MF than in healthy people, and this was true regardless of the patients blood tumor burden. While this innovative study does not fully explain the importance of the MF-derived exomiRNA, the findings, suggest a direct translational application in clinics. 

Both cfmiR-155 and cfmiR-1246, as well as exomiR-1246, should be considered as MF-associated molecular indicators for advanced skin disease. They could serve as novel therapeutic targets and pave the way for the development of new diagnostic techniques, such as liquid biopsy for CTCL.

Source: The British Journal of Dermatology. 2021 Nov;185(5):884-886. doi: 10.1111/bjd.20695.