Molecule That Could Improve Cancer Vaccines

Scientists have discovered a new signaling molecule that prevents immune responses from running amok and damaging the body and could lead to the development of new treatments for cancer (using vaccines), for autoimmune diseases(Type 1 diabetes), for inflammatory diseases bowel disease and asthma.

Specialized immune lymphocytes (regulatory T cells) release a protein complex composed of two proteins: Ebi3 and Il12a wich acts like a brake on the activity of the aggressive immune cells (effector T lymphocytes).

This protein complex is one of a large group of signaling molecules – cytokines – that cells use to communicate with each other. Since the immune system cytokines are called interleukins, this protein name is interleukin-35 (IL-35). Most cytokines stimulate immune system cells by driving the immune attack or causing inflammation. IL-35 is one of the few signaling molecules known to inhibit immune system activity.

The discovery of Interleukin-35 is important because the manipulation of regulatory T cells is a key goal of immunotherapy wich means the treatment of infections, cancer or other diseases by manipulating the immune system to enhance or restrict its activity. Despite the fact that regulatory T cell-mediated immunotherapy holds promise for patients, the molecules responsible for the cells’ ability to suppress immune system activity are largely unknown.

Scientists showed that Ebi3 and II12a are active in regulatory T cells but not in effector T cells and are critical to regulatory T cell function. These regulatory T cells are unable to cure mouse models of an inflammatory disease that closely resembles human inflammatory bowel disease.

When the Scientists added regulatory T cells to a culture dish with effector T cells, the regulatory T cells dramatically increased their production of the decoded forms of the Ebi3 and II12a genes. This suggests that effector T cells had released signals that stimulated the regulatory T cells to decode these genes and make IL-35, the researchers reported.

Regulatory T cells are a impediment to the development of effective anti-cancer vaccines and may prevent sterilizing immunity in certain chronic infections, for exemple hepatitis C, tuberculosis. Vaccines work by stimulating the immune system to recognize and attack specific targets, such as germs or cancer cells.

Autoimmune and inflammatory diseases are caused by a breakdown of the normal regulatory processes that control our immune system.

The identification of IL-35 is the only known cytokine that is made specifically by regulatory T lymphocytes and can suppress the activity of effector T cells directly. This suggests that controlling levels of IL-35 in patients might one day allow clinicians to dial the immune response up or down.