Immunosuppressive Effects of Adenosine Through Multiple Pathways
The Adenosine-Cancer Axis and Anti-tumor Immune Response
Adenosine is a signaling molecule used by the body to limit inflammation and immune responses. Many different types of tumors produce and actively sustain high levels of adenosine within the tumor microenvironment. One of the ways that tumor cells produce adenosine is by expressing high levels of an enzyme on their surface called CD73. CD73 generates adenosine, and this contributes to the maintenance of high levels of adenosine in the tumor microenvironment.
Adenosine hinders the ability of the immune system to attack the tumor, mainly in two ways: (1) by blocking the activation and effectiveness of immune cells that are capable of destroying tumor cells, and (2) by increasing the number of regulatory T-cells (T-regs) that act to suppress immune cells from responding to the tumor. As tumor cells evolve and form cancerous growths, they utilize these processes to evade immune attack and promote their own survival.
The adenosine that tumors produce interacts with adenosine receptors on the surface of invading immune cells. A type of adenosine receptor known as A2A is expressed on several cells of the immune system, including T-cells, NK cells, macrophages and dendritic cells. Binding of adenosine to the A2A receptor has the effect of dampening the ability of the immune cells to attack tumors. A significant body of scientific data indicates that targeting the adenosine-cancer axis through the A2A receptor can promote anti-tumor immune responses to occur, leading to tumor regression.