An emerging class of therapies called “checkpoint blockade” enhance the immune system’s ability to attack cancer cells by interfering with the immunological checkpoints that slow or stop immune cell activation and proliferation in the presence of tumors. Cytotoxic T lymophocyte antigen-A (CTLA) receptor is a protein that acts like an “off switch” on certain immune cells. Antibodies targeting CTLA can keep the protein from turning the immune cells off and allow them to attach tumor cells.
In this issue of the Journal of Clinical Investigation, Sandra Demaria and her colleagues at New York University identified factors that determine the effectiveness of anti-CTLA therapy by tracking the activity of immune cells in a mouse model of breast cancer. In this model anti-CTLA therapy alone was ineffective. When given in combination with radiation treatment, however, tumor growth and mestastases was significantly reduced. The researchers found that the radiation therapy caused the cancer cells to release a protein, NKG2D, which activates the immune cells and attracts them to the tumor. These findings will be critical in developing improved treatment regimens utilizing CTLA antibodies.
“Suppressing T cell motility induced by anti–CTLA-4 monotherapy improves antitumor effects” Sandra Demaria, New York University School of Medicine, New York, NY, USA
Journal of Clinical Investigation Sept. 4, 2012