Summary of work Parker Institute researchers at the UCLA Jonsson Comprehensive Cancer Center, led by Catherine Grasso, PhD, have discovered genetic mutations that may explain how some colorectal cancers hide from the immune system, making them resistant to immunotherapy treatment. Working with investigators at the Broad Institute, Dana-Farber Cancer Institute and Fred Hutchinson Cancer Research Center, the team analyzed more than 1,200 colon cancer samples, focusing on a subset of highly mutated tumors known as microsatellite instability-high or MSI-high tumors. Significant findings were three-fold: 1. Certain mutations in genes B2M, HLA, Tap2, NLRC5 help the cancer avoid immune detection; 2. Some cancers are innately resistant before treatment; 3. A therapeutic target called the WNT pathway could enhance immunotherapy response. Other Parker Institute researchers involved in the study include Antoni Ribas, MD, PhD, Danny Wells, PhD and Jesse Zaretsky, PhD. Why this is impactful to patients “What was significant is that they identified new genetic clues that explain how certain colorectal cancers are able to avoid being recognized and attacked by the immune system, limiting the effectiveness of immunotherapy,” says Fred Ramsdell, PhD, vice president of research at the Parker Institute. “The findings also suggest there might be new approaches for tackling colorectal cancer, which remains difficult to treat.” Colorectal cancer is the third most diagnosed cancer in the United States, according to the American Cancer Society.