Mutations in cancer-suppressing genes that block cell growth may explain why some cancers evade the body’s immune system, scientists have established. A US team has identified 100 “mutated tumor suppressor genes” that affect the body’s ability to spot and destroy cancer cells in mice. While at an early stage, identifying genetic mutations could lead to the creation of new targeted therapies, the authors believe.
Scientists have struggled to understand why the body’s immune system doesn’t attack abnormal cells, such as cancer. Theories have suggested that mutations in cancer-suppressing genes enable cancer cells to grow uncontrollably, but such action hasn’t been observed in laboratory tests.
To learn more about the function of cancer-suppressing genes, Stephen Elledge, a Howard Hughes Medical Institute Investigator at Brigham and Women’s Hospital, probed over 7,500 genes. “The shock was that these genes are all about getting around the immune system, as opposed to simply saying ‘grow, grow, grow!’” said Elledge.
To understand the function of specific genes, the team engineered tumours but removed one of the genes. Scientists then introduced the tumours into mice with and without an immune system to see if and how the tumours grew. In results published in the journal Science, investigators describe how they identified several mutated genes in tumours, suggesting a role in tumour formation. In 30% of cases, tumour suppressing genes actually worked to enable the tumour to evade the immune system.
To explore further, the team focused their attention on the GNA13 gene. A mutation in this gene protects cancer from T-cells that would typically target it. Elledge’s research suggests that there are hundreds of ways that a tumour can attempt to evade detection. “There are a lot of genes that people can now study,” he says. However, he suggests that the mechanisms they use are likely to be similar, raising hopes of new targeted treatments.
The research also sheds light on why checkpoint inhibitors may not be as effective for some patients. Checkpoint inhibitors work by blocking proteins that “switch off” the immune system and boost the body’s ability to fight back. While offering huge potential, some patients may experience significant side effects, and for others, they may not work at all. Elledge’s findings could provide exciting new avenues for research, although this is at an early stage.
RGCC scientists are at the forefront of developing new treatments for cancer, including gaining approval for clinical trials on a new product, VAXO-Q-Re. It’s the latest in a pipeline of advanced cancer therapies developed by RGCC scientists, says founder and CEO Dr Ioannis Papasotiriou.
Alongside developing advanced cancer therapies, RGCC offers a range of personalised genetic tests that can help improve the diagnosis and treatment of cancer. Our tests are only available through our trusted global RGCC network.
You can read the full paper The adaptive immune system is a major driver of selection for tumor suppressor gene inactivation, here.