Identification of Novel Genes Important for Immune System Escape by Cancer Cells Using CRISPR

Release Date: 25-Nov-2020

A group of researchers from the University of Toronto in collaboration with the researchers from Agios Pharmaceuticals are focused on using CRISPR technology to screen six different genetically driven mouse cancer cell lines. It was found by the researchers that some of the genes that are involves in autophagy were the important key for the evasion of the immune system. As per the researchers who were inclined towards the clinical research study, it was important to understand the molecular level of how cancer cells develop resistance to different immunotherapies.

Therefore, the researchers involved in the clinical research study were more focused towards using CRISPR-Cas9 technology for the overall screening of the cancer cells that were further cultivated in the absence or presence of T killer cells. It was found by the researchers, that there are 182 genes that when mutated, deleted, resulted in changed resistance of the cancer cells towards T cells. It was also witnessed that the genes that were found by the researchers also affected signalling of the interferon gamma, which is believed to be important for generation of immune responses. Some of the negative regulators of the signalling of the interferon gamma are: Socs1, Ptpn2 and Adar. Among all the genes that were identified for autophagy, Fitm2 gene was found to be most important.  

As per the research conducted in the mouse models suffering from renal cell carcinoma and melanoma, the cancer cell that had deleted Fitm2 resulted in increased cell death rate prior treatment with interferon gamma when compared with the cell death rate in control cell. In addition to this, researchers also found that the deletion of various autophagy genes led to resistance development in cancer cells against T cell killing. The researchers involved in the respective study need to focus on the future clinical work so that it could be developed as a novel potential treatment regimen for the cancer patients.