In a new study entitled “Neuroblastoma Arginase Activity Creates an Immunosuppressive Microenvironment That Impairs Autologous and Engineered Immunity” scientists at Cancer Research UK unveiled a new mechanism that allows neuroblastoma tumor cells to block immune cells’ proliferation and prevent their activity against cancer cells. The study was published in the journal Cancer Research.
Neuroblastoma is a cancer that develops from immature nerve cells and is the most common extracranial solid cancer in children (aged 5 years or younger). As other types of cancers, neuroblastoma cancer cells exhibit specific molecules at their surface, distinguishing them from normal, healthy cells. Novel immune therapies were developed to target these specific molecules and enhance patients’ immune system action against tumors. However, patients’ clinical outcomes have failed to match the results from pre-clinical studies.
In this study, scientists at Cancer Research UK exploited the mechanism behind these unsuccessful results. They discovered that neuroblastoma tumor cells block T cells’ proliferation by increasing the activity of arginase. This increase leads to the breakdown of arginine, a key amino acid and energy source for the body’s immune cells. Hence, neuroblastoma cancer cells create an immunosuppressive microenvironment, not only in the tumor but also in the blood, with clinical data showing that arginase increased expression is associated with neuroblastoma patients’ poor survival outcomes.
Dr. Francis Mussai, study first-author commented, We’ve known for a while that harnessing the power of the immune system could be an effective way to treat neuroblastoma. But we didn’t know why the immune cells were having such difficulty recognising and destroying the tumour. Armed with this new knowledge about the role of arginine, we may be able to activate the immune system to attack cancer cells.”
Dr. Carmela De Santo, University of Birmingham and one of study lead authors added, “Now the challenge is to develop new drugs which stop neuroblastoma from using arginine, and may make immune therapy more effective.”
These findings are the foundation for developing drugs that can block arginase activity in neuroblastoma cancer cells, as Eleanor Barrie, senior science information manager at Cancer Research UK noted, “These findings could have huge implications for treating neuroblastoma. Better understanding the role of arginine could help us to boost the body’s immune cells and we hope this could lead to more effective treatments. We recently launched Cancer Research UK Kids and Teens as part of our commitment to bringing forward the day when no young lives are lost to cancer. Our target is to find more cures and kinder treatments for children with the disease so that, in the future, every child with cancer can go on to live a long and healthy life.”