Re-exposing a cancer protein to enhance immunotherapy

Credit: Victor Segura Ibarra and Rita Serda, PhD, National Cancer Institute, National Institutes of Health/CC BY-NC 2.0 DEED

Successful immunotherapy for cancer involves activating a person’s own T cells to identify telltale proteins called antigens on the surface of a tumor and attack it. But some tumors have a trick: They hide themselves from the immune system by preventing their antigens from being displayed. A team led by Harvard Medical School researchers at Boston Children’s Hospital has now found a way around this defense in mice.

The findings suggest a strategy for developing add-on treatments that make cancer immunotherapies more effective. The key lies in a protein called prosaposin, the team reported in Science. Tumor tissue contains a large percentage of dying cells that shed little capsules, or vesicles, containing the tumor antigens. Immune cells called dendritic cells absorb these vesicles, process the antigens, and sprout pieces of the antigens on their surface, which teaches T cells to recognize and attack the antigens. The researchers found that without prosaposin, dendritic cells can’t break down the vesicles and present the tumor antigens to the immune system as a teaching tool. Specifically, the dendritic cells need proteins called saposins that form from prosaposin, the team discovered.

“We found that saposins are needed to digest these vesicles and free the tumor antigen for display to the immune system,” explained senior author Florian Winau, HMS associate professor of pediatrics in the Program in Cellular and Molecular Medicine at Boston Children’s.

By Nancy Fliesler, Harvard Medical School

Article can be accessed on: MedicalXpress