Design of the CRISPR-based screen. Anti-tumor T cells kill a target cancer cell (top panel). Disruption of a target gene reduces or eliminates the ability of cytotoxic T cells to vanquish the tumor (bottom panel).SHASHANK PATEL, NCI, NIH Immune checkpoint inhibitor antibodies are a relatively new class of cancer drugs that are now approved to treat patients with late-stage melanoma and those with certain lung, bladder, head and neck, kidney, and other types of late-stage cancers. Some patients respond and go into long remissions when treated with these therapies, while others fare worse.
Using a genome-wide CRISPR-based screen, researchers at the National Cancer Institute (NCI) and their colleagues identify protein-coding genes that must be expressed by a tumor in order for this type of cancer immunotherapy to work. The results are published today (August 8) in Nature.
“This is an elegant study and a novel application of CRISPR library screening,” says Drew Pardoll, director of the Johns Hopkins Bloomberg-Kimmel Institute for Cancer Immunotherapy who was not involved in the work. “The study validates genes we knew [were necessary] for tumors to respond to immunotherapy and turns up a number of unexpected, potentially interesting genes.”
Focusing on CD8+ effector T-cells—the immune cells activated by immunotherapies based on immune checkpoint inhibition—the authors wanted to identify the genes that, when mutated, ...
