Project leader: Delphine Fradin CR2 Inserm

A better understanding of mechanisms of immune evasion by cancer cells and the role of the tumor microenvironment is crucial for developing new effective cancer therapeutic strategies. The challenge is posed by the enormous complexity of both the immune system and the tumor microenvironment, and the intricate cancer–immunity signaling network.
Among regulation mechanisms, the role of extracellular vesicles, such as the exosomes, released by cancer cells in tumor microenvironment appears to be a mechanism used by tumor cells to disseminate bioinformation in autocrine and paracrine manner. These endosome-derived vesicles of ∼30–100 nm are formed in the multivesicular bodies and then released from the cell into the extracellular space. They carry a broad range of cargo, including proteins, noncoding RNAs* (ncRNAs), mRNAs, and DNA fragments, to target cells. Upon entering the target cell, the exosomes induce modulation of cell function and even identity switch (phenotypic and epigenetic).

We are focusing on exosomal noncoding RNA content (miRNA and lncRNA) transferred to immune cells and further examine their ability to alter immune response.

A non-coding RNA (ncRNA) is a functional RNA molecule that is transcribed from DNA but not translated into proteins. Epigenetic related ncRNAs include miRNA, siRNA, piRNA and lncRNA. In general, ncRNAs function to regulate gene expression at the transcriptional and post-transcriptional level. Those ncRNAs that appear to be involved in epigenetic processes can be divided into two main groups; the short ncRNAs (<30 nts) and the long ncRNAs (>200 nts). The three major classes of short non-coding RNAs are microRNAs (miRNAs), short interfering RNAs (siRNAs), and piwi-interacting RNAs (piRNAs). Both major groups are shown to play a role in heterochromatin formation, histone modification, DNA methylation targeting, and gene silencing.