Extracellular microRNAs in the tumor microenvironment

The human immune system serves as an important surveillance system for protecting against cancer cells and the formation of tumors. Hence for a tumor to form, cancer cells need to develop strategies for evading this protective mechanism and keep the immune system in a non-active state. Understanding and manipulating these interactions to generate a re-activation of cancer targeting immune cells has led to a new class of cancer treatments called immunotherapies. MicroRNAs are a special class of small non-coding RNA molecules that have been previously implicated in the development of cancer. This class of small RNAs plays an important role in regulating gene expression post-transcriptionally by interfering with the translation of mRNAs. More recently it has been discovered that microRNAs can also travel outside of cells, and extracellular microRNAs (exmiRNAs) have gained a lot of interest as potential new vehicles of intercellular communication. Nevertheless, the importance of exmiRNAs in intercellular communication is still controversial, largely because exmiRNAs are only present at low concentrations in biofluids and it is experimentally challenging to conclusively demonstrate the transfer of RNA molecules from one cell to another. Interestingly, new discoveries about mammalian microRNA biology have revealed that microRNAs are not constantly active but are required during certain physiological responses such as the regeneration of tissues and the activation of the immune system. Hence, immune cells could be particularly vulnerable for getting reprogrammed by microRNAs released by cancer cells in the tumor microenvironment. Developing new strategies for monitoring the transfer of microRNAs between cells and deciphering the role of exmiRNAs in modulating the activity of immune cells in the tumor microenvironment will be the goal of this project.