How Cancer Cells Evade the Immune System

Researchers at Howard Hughes Medical Institute have discovered that many genes linked to human cancer block the body's natural defense against cancer.

"The shock was that these genes are all about getting around the immune system, as opposed to simply saying 'grow, grow, grow!',” says lead researcher Stephen Elledge in a press release issued by Howard Hughes Medical Institute.

"These results reveal a fascinating and unexpected relationship between tumor suppressor genes and the immune system," says a Johns Hopkins University cancer geneticist who was not involved in the research work.

A research paper is published in Science. It reveals that more than 100 mutated tumor suppressor genes can prevent the immune system from spotting and destroying malignant cells in laboratory mice.

The researchers wanted to check whether defective tumor suppressor genes were doing something more than helping cancer cells to grow. Starting with a list of 7,500 genes, the researchers used CRISPR to engineer thousands of tumor cells. Each engineered tumor cell lacked a functioning version of one of those genes.

The researchers put the cells into two types of laboratory mice. The first type was those with a functioning immune system. The second was those without. Then, the researchers studied the tumors that grew.

The researchers analyzed which mutated genes were abundant in the tumors. In mice with functioning immune systems, the defective tumor suppressor genes showed up frequently. This suggests that those genes, which amount to about 30 percent of all tumor suppressor genes tested, work by enabling tumors to evade the immune system.

It appears that many different genes can mutate to help cancer escape the immune system. And this is likely to play a role in the formation and growth of cancer.

To explore possible mechanisms triggered by the mutations, the researchers investigated a gene called GNA13 in more detail. They found that mutating the gene protects cancer cells from the immune system's T-cells. And that creates a safe space for the tumor to thrive.

Elledge explains that there seems to be a quick and fierce evolutionary arms race between cancer cells and the immune system, with tumors having hundreds of potential ways to foil the body's attack. But Elledge suspects that many of these mutated genes act via similar strategies, a possibility his team can now examine in detail. If this proves to be the case, an intervention to block one evasion technique could potentially thwart others as well.

"There are a lot of genes that people can now study," concludes Elledge.

I hope further study will unveil the role played by different genes in protecting cancer from the immune system. And I hope that will help us find new genetic therapies to fight cancer.