The rise of immunotherapy has been one of the most startling and promising developments in cancer research for some time. After decades of false starts and dead ends, scientists have finally found effective ways of marshaling the immune system to destroy cancers. Some use drugs called “checkpoint inhibitors” to lift the natural brakes that restrain immune cells, allowing them to go to town on tumors. Others are extracting, engineering, and re-injecting the immune cells themselves. The results have been staggering. Advanced cancers have gone into complete remission. People who were given months to live are still here years later.
But immunotherapy isn’t a panacea. For the moment, it only works for some types of cancer. Even then, only about 20 percent of patients respond. When these treatments work, they work really well—but they don’t always work. Why? To answer that, Sergio Quezada at University College London and Charles Swanton at the Crick Institute realized that they needed to answer a simple question: How does the immune system see tumors, and what are they actually seeing?
As tumors expand, they accrue mutations in their genes that fuel their growth, and that distinguish them from normal, healthy cells. These mutations also change molecules called neoantigens that are displayed on the surface of the tumor cells. To our immune system, neoantigens are red flags that say “There’s something weird, foreign, other about these cells.” It responds by producing targeted weapons—T-cells that specifically recognize the neoantigens and attack whatever carries them.