Therapeutic strategies that use the immune system to fight tumors, enhance the effectiveness of cancer treatment. Among the most successful type of immunotherapy is allocated class checkpoint inhibitors, which "expose" the tumor lurking of immunity. However, checkpoint inhibitors are not suitable for all types of cancer.
Research at the University of Colorado Cancer Center conducted a study that reveals the mechanisms of action of triple negative breast cancer. Scientists have told us how the process of initiation, which allows the disease "hide" for immune cells.
Identification of the mechanisms underlying the "invisibility" of cancer cells may help in the development of more effective therapeutic strategies.
The story begins (or, technically, ends) with a protein called PD-L1. Many types of cancer cells have learned to hide under this protein as a "cloak" to avoid the attack of immune cells. Immunotherapy using checkpoint inhibitors, blocks the ability of PD-L1 to interact with PD-1 protein, detected on T cells, which allows immunity "see criminals".
As cancer cells initiate the production of PD-L1?
Research scientists from the Cancer Center have tried to answer this question. To understand the results of their work, we need to "move away" from the end point of PD-L1 and take a look at another genetic "Player» - Eya3.
"Studies have shown that Eya3 involved in the immune response to the virus, but no one has studied whether Eya3 involved in evasion of cancer cells from the immune system," - said Heide Ford, deputy director of the Cancer Research Center.
Eya family of proteins which includes Eya3, a research center in Ford Laboratory. Basically, Eya proteins are involved in early embryonic development, and most of them are "silent" in the tissues of an adult organism. Studies have shown that cancer can renew Eya proteins, and they lead to the growth and spread of cancer cells.
Eya are complex molecules consisting of separate regions, each having its own function. But none of the scientists had not considered the effect of different areas Eya inside or outside the cell. In order to understand how proteins Eya affect the interaction of the tumor with the host's immune system, researchers from the University of Colorado Cancer Center used the immunocompetent mouse model transplanted withbreast tumorsthat mimic human breast cancer. This allowed the scientists to examine not only what is going on inside living cells, but also how these living cells interact with their mikrooruzheniem.
Action protein Eya3
"We found that Eya3 can regulate the immune response to a tumor" - said Heide Ford.
Scientists have demonstrated that inhibition of the ability of cancer "awaken" Eya3 cells led to reduced production of PD-L1 and increasing the infiltration of killer T cells (CD8 + T-cells). In other words, if the tumor could not create Eya3, she could not create and PD-L1. As a result, the immune system has been successfully attacked by cancer.
Researchers have noted that Eya3 is a key regulator of PD-L1 and potentially main driver PD-L1, however, there are other methods of protein regulation.
The study was published in the «Journal of Clinical Investigation» magazine.