August 31, 2017
Certain genes are essential in cancer cells for immunotherapy to be effective, according to a new study published online in Nature (doi: 10.1038/nature23477).
“There is a great deal of interest in cancer immunotherapy, especially for patients who have metastatic cancer,” said Nicholas Restifo, MD, a senior investigator at the National Cancer Institute, in an institute press release (August 7, 2017). “The response to immunotherapy can be fantastic, but understanding why some patients don’t respond will help us improve treatments for more patients.”
Cancer immunotherapy relies on T cells from the immune system to recognize and kill tumor cells. However, some tumor cells are resistant to T cells. This study aimed to identify genes in cancer cells that are necessary for T cells to be able to destroy tumors.
Using gene editing technology to knock out individual genes in cancer cells and then testing the ability of the modified cancer cells to respond to T cells, researchers identified more than 100 genes that may play a role in successful tumor destruction by T cells. Next, researchers looked at data for more than 11,000 patient tumors and found additional evidence that a number of the genes were indeed linked with tumor cytolytic activity — a genetic profile that shows cancer cells are responding to T cells — in patient samples.
“Many more genes than we originally expected play a vital role in dictating the success of cancer immunotherapies,” said study first author Shashank Patel, PhD.
This gene list, researchers explained, could be used as a blueprint to investigate the emergence of tumor resistance to immunotherapy. If the gene list is validated in clinical trials, the information could lead to more effective treatments.
“If we can truly understand mechanisms of resistance to immunotherapy, we might be able to develop new therapeutics,” said Dr Restifo. “In fact, in the future, this knowledge could speed the development of a new category of drugs that can circumvent these escape mechanisms of tumor cells and help patients experience complete responses.”