This webinar provides an overview of genomic alterations that play a role in immunotherapy response.
Impressive response rates to checkpoint inhibitors have been observed in subsets of tumors with high tumor mutational burden due to mutations in DNA polymerase epsilon (POLE) and mismatch repair genes (MMR) across histologies. Mutations in the MMR pathway lead to microsatellite instability (MSI), which is characterized by alterations in the length of repeated DNA microsatellite sequences. The MSI phenotype was originally described for inherited tumors associated with Lynch syndrome and was later identified in sporadic tumors. The prevalence of MSI is higher in colorectal, endometrial, and gastric cancers, but MSI has been observed in many tumor types at varying frequencies.
In this webinar, Dr. Michael Overman of the University of Texas MD Anderson Cancer Center discusses the molecular mechanisms of immunotherapy response. In particular, he provides evidence that MSI-high and other hyper-mutated tumors have large numbers of neoantigens to which the immune system can respond when primed by checkpoint blockade.