In a recent discovery by University of Minnesota (U of M) Medical School, researchers uncovered a new way to potentially target and treat late-stage colorectal cancer – a disease that kills more than 50,000 people each year in the United States. The team identified a novel mechanism by which colorectal cancer cells evade an anti-tumor immune response, which helped them develop an exosome-based therapeutic strategy to potentially treat the disease. “Late-stage colorectal cancer patients face enormous challenges with current treatment options. Most of the time, the patient’s immune system cannot efficiently fight against tumors, even with the help of the FDA-approved cancer immunotherapies,” said Subree Subramanian, PhD, an Associate Professor in the U of M Medical School’s Department of Surgery and a senior author of the study. In partnership with Xianda Zhao, MD, PhD, a postdoctoral fellow in Dr. Subramanian’s laboratory, the duo set out to investigate how colorectal cancer becomes resistant to available immunotherapies. What they found was recently published in Gastroenterology, including: (1) Colorectal cancer cells secrete exosomes that carry immunosuppressive microRNAs (miR-424) that actually prevent T cell and dendritic cell function because they block key proteins (CD28 and CD80) on these immune cell types, respectively. In the absence of these proteins, the T cells, which would normally kill the cancer cells, become ineffective and are eliminated from tumors, allowing tumors to grow. (2) By blocking these immunosuppressive microRNAs in cancer cells, the team observed an enhanced anti-tumor immune response and discovered that cancer cell-secreted exosomes also contain tumor-specific antigens that can stimulate the tumor-specific T cell response.
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