NCI Study Identifies Essential Genes for Cancer Immunotherapy

A new study identifies genes that are necessary in cancer cells for immunotherapy to work, addressing the problem of why some tumors don’t respond to immunotherapy or respond initially but then stop as tumor cells develop resistance to immunotherapy.

The study, from the National Cancer Institute, was led by Dr. Nicholas Restifo, a senior investigator with the Center for Cancer Research, with coauthors from NCI, Georgetown University, the Broad Institute of MIT and Harvard University, New York University and the University of Pennsylvania. It was published online in Nature on Aug. 7.

“There is a great deal of interest in cancer immunotherapy, especially for patients who have metastatic cancer,” said Restifo. “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, a type of cell in the immune system, to destroy tumors. Restifo and his colleagues have previously shown that the infusion of large numbers of T cells can trigger complete regression of cancer in patients. They and others have also shown that T cells can directly recognize and kill tumor cells.

However, some tumor cells are resistant to the destruction unleashed by T cells. To investigate the basis for this resistance, the researchers sought to identify the genes in cancer cells that are necessary for them to be killed by T cells.