Neoepitopes of Cancers: Looking Back, Looking Ahead.

The search for specificity in cancers has been a holy grail in cancer immunology. Cancer geneticists have long known that cancers harbor transforming and other mutations. Immunologists have long known that inbred mice can be immunized against syngeneic cancers, indicating the existence of cancer-specific antigens. With the technological advances in high-throughput DNA sequencing and bioinformatics, the genetic and immunologic lines of inquiry are now converging to provide definitive evidence that human cancers are vastly different from normal tissues at the genetic level, and that some of these differences are recognized by the immune system. The very vastness of genetic changes in cancers now raises different question. Which of the many cancer-specific genetic (genomic) changes are actually recognized by the immune system, and why? New observations are now beginning to probe these vital issues with unprecedented resolution and are informing a new generation of studies in human cancer immunotherapy.