For decades, researchers have worked to understand how the mutations found in malignant cells drive cancer. The vast majority of research has focused on mutations that help cancer cells grow and survive, with most cancer therapies developed thus far geared toward disrupting these pathways.

However, Elledge explains, there’s been an increasing awareness that cancer cells must also overcome attacks from the immune system, which initially treats cancer cells like pathogens and unleashes a response to eliminate them.

To avoid these attacks, cancer cells develop mutations that allow them to masquerade as healthy cells or take advantage of systems already in place that regulate immunity to prevent autoimmune disease.

Some cancer therapies—such as checkpoint inhibitors, a class of cancer immunotherapies first approved by the FDA in 2011—take aim at these mechanisms in an effort to make the immune system regain effectiveness against cancer. But, thus far, these drugs have been successful only for some forms of cancer, and even then in only a fraction of patients.

Elledge and his colleagues suspected that the pathways targeted by these existing drugs might represent only a few of many that cancer cells use to evade the immune system.