Sumary of Study shows how melanoma cells evade detection and destruction by immune cells:
- Several therapeutic strategies to activate the immune system to target cancer cells have been approved to treat different types of cancer, including melanoma..
- However, some patients do not show beneficial clinical responses to these novel and very promising immunotherapies..
- In a new article published in Proceedings of the National Academy of Sciences of the United States of America, Moffitt Cancer Center researchers demonstrate how an important defect in STING gene expression in melanoma cells contributes to their evasion from immune cell detection and destruction..
- Several different mechanisms have been discovered that allow cancer cells to avoid immune cell detection and destruction, including defective T cell function, losses in expression of key proteins on tumor cells and defective cell signaling in both immune and tumor cells..
- Moffitt researchers previously demonstrated that STING activity is commonly suppressed and altered in a subset of melanomas, which prevents the ability of these tumor cells to be targeted by the immune system..
- They focused on a process called epigenetic modification during which methylation groups are added to the DNA regulatory regions of genes, resulting in genes being turned off..
- Related Stories The researchers performed a series of laboratory experiments and discovered that the DNA regulatory region of the STING gene is highly modified by methylation groups resulting in loss of STING gene expression in certain melanoma cell lines..
- Importantly, they confirmed these findings in patient clinical samples of early and late-stage melanomas and showed similar methylation events and loss of expression of the upstream STING regulator cGAS..
- Next, the researchers demonstrated that it is possible to reactivate expression of STING and/or cGAS with a demethylating drug or genetic approaches that overcome methylation….