In Cancer Immunotherapy, More Mutations in Cancer Cells Isn’t Necessarily Better

DNA mismatch repair deficiency (MMRd) is a genetic condition often associated with colon cancer. It can happen in otherwise normal cells before cancer forms or after a tumor has already formed. The condition makes it hard for cells to correct mistakes that occur in DNA copying. This can lead to many mutations within tumors, or a high tumor mutation burden (TMB). Some patients with high TMB respond well to immunotherapy, which uses the body’s own immune system to fight cancer cells. But immunotherapy doesn’t work for more than half of patients with advanced MMRd tumors. Now, research from Cold Spring Harbor Laboratory (CSHL) Assistant Professor Peter Westcott, PhD, and colleagues may help explain why. The results were published on September 14, 2023 in Nature Genetics. The open-access article is titled “Mismatch Repair Deficiency Is Not Sufficient to Elicit Tumor Immunogenicity.” MIT’s Tyler Jacks, PhD, is the senior author of the article.