Nobel Week 2018 traditionally started with the award in the field of physiology and medicine. It was divided between American immunologist James Patrick Allison and Japanese immunologist Honjo Tasuku, who laid the foundation for new cancer treatments.
From the late 1990s both scientists investigated the mechanisms that allow cancer to remain invulnerable to the immune system. It turned out that the tumor ‘hides’ from T-lymphocytes using the so-called ‘checkpoints’ of the immune response, which are the molecules that normally protect healthy cells from the immune attack.
James Patrick Allison, a professor at University of Texas, deciphered the structure of one of these ‘checkpoints’ — CTLA-4 protein, which is located on the surface of T-cells. This protein is involved in the interaction of lymphocytes with antigen-presenting cells, which act as ‘beacons’, pointing out what the other components of the immune system should react to. When CTLA-4 binds to proteins on the surface of such cells, they become deactivated and stop sending signals. As a result, the object on which the attack could have been targeted avoids the attention from the immune system. This is the exact mechanism cancer cells use to stay unnoticed.
The PD-1 receptor protein, discovered by professor at Kyoto University Honjo Tasuku, is also located on the surface of T-cells. PD-1 serves as a kind of ’emergency brake’, stopping the attack of lymphocytes on certain cells. It must bind to a specific molecule on the surface of the cell to start working. This may be PD-L1, which is representative of tumor cells.
Having determined the protection mechanism of tumors, the researchers were able to outwit it by inhibiting the work of CTLA-4 and PD-1 proteins. This allows the immune system to attack the malignant cells at full power. The discovery has already become the basis for new drugs against lung, kidney and skin cancer.