A new study has found that mutations in Ras genes can not only allow tumor cells to multiply and spread, but can also protect them from the immune system. The work was published in Immunity yesterday and comes from researchers at the Francis Crick Institute and Institute of Cancer Research (ICR), London.
In this study, the researchers showed that mutated Ras genes can suppress the immune system around tumors by increasing levels of a protein called PD-L1. Small amounts of PD-L1 exist naturally in the body to prevent the immune system from attacking healthy cells, but cancer cells can exploit this to protect themselves.
To show this link between Ras and PD-L1 levels, mice with Ras mutant cancers were given compounds to counteract the effects of Ras signaling on PD-L1 expression. They found that their tumors were attacked by the immune system, slowing tumor growth.
"Our study highlights the fundamental role that Ras mutations play throughout the different stages of cancer," explains senior author Julian Downward, Group Leader at the Francis Crick Institute and Head of the Lung Cancer Group at the ICR. "We already knew that they played a key role in starting around a quarter of all human cancers, causing cancer cells to grow, multiply and spread. We now know that they also help to protect the cancer cells from our immune systems, making them more difficult to treat. Understanding the mechanisms behind this will help us to develop better treatments in future, for example boosting immunotherapy approaches with drugs that disrupt cancer's defenses."