Interleukin 22 (IL-22)

Usually, wherever MDSCs are there is a protein that seems to be present in large amounts: Interleukin-22 (IL-22). Furthermore, the production of IL-22 is tightly regulated and is triggered by viral infection, which is consistent with what is known about the function of MDSCs (Yi et al, 2017). IL-22 is often linked to inflammatory conditions, especially in the gut and liver. Inflammation occurs when the immune system tries to terminate a chronic infection and inflammatory cytokines are released, an instance in which MDSCs are heavily involved (Veglia, Perego & Gabrivolich, 2018). Similarly, during pathologies that involve MDSCs, such as h. pilori infection, gut infection, and autoimmunity, IL-22 is correlated to present in high amounts. Unfortunately, while the relationship between IL-22 and MDSCs is clear, it is relatively unexplored. It is hypothesized that MDSCs use the IL-22 protein to communicate with each other and the Tregs and T Cells they regulate.  

In order to study the effect of IL-22 gene in cancer cells, CRISPR will be used. CRISPR would allow the removal of the gene, which would allow the study of how MDSCs’ reaction to cancer cells would change. Clustered regularly interspaced short palindromic repeat (CRISPR) is a genome-editing tool, revolutionary in its inexpensiveness and effectiveness. CRISPR is able to cut DNA at specific places, then add or delete specific strands (Pak 2014). The DNA is then reintroduced into a cell, where it is hopefully accepted. This enables entire genes to be taken out, allowing scientists to completely modify an organism, by deciding which proteins will be made and which ones will no longer be produced. This research will use CRISPR to change the genes of a 4T1 cell. If the gene deletion is successful, and the 4T1 cells reincorporate the modified plasmid, the syngeneic nature of the 4T1 cells will allow us to reinsert the cells and monitor the effect of the modification.

Goals and research overview

The goal of this project is to analyze the relationship between IL-22 and MDSCs to possibly improve cancer immunotherapy. This is based on the proven theory that cancer cells use MDSCs to protect themselves. It is theorized that MDSCs use IL-22 to communicate with cancer, which will be studied by using CRISPR to remove the IL-22 gene from 4T1 cancer cells. If IL-22 plays a significant role in the manipulation of MDSCs, the removal of the gene will result in a decrease in the number of MDSCs near a tumor. Conversely, if IL-22 is not involved in communicating with MDSCs, it’s removal will have no effect on the concentration of MDSCs near a tumor. If IL-22 is responsible for MDSC communication, once it is removed from the genome of a 4T1 cell, MDSCs will no longer be present in a significantly high concentration around a tumor.