For General Public

It is estimated that approximately 3,000 abnormal cells (cancer cells) are produced in our body every day. Normally, our body’s immune system prevents the development of cancer. However, when these cells achieve immunosuppression by using immune checkpoint molecules to evade the immune system, they acquire malignancy which in turn develop cancer.

CCII Director Prof. Tasuku Honjo received the Nobel Prize in Physiology or Medicine in 2018 for his contribution in identifying the mechanisms of immunosuppression and developing immunotherapy by inhibiting immune checkpoint molecule PD-1 (programmed cell death-1). PD-1, discovered to be central to immunosuppression, is a key immune checkpoint molecule and often expressed among activated killer T cells. PD-L1, the ligand of PD-1, on the other hand, is often expressed in cancer cells. Through the binding of PD-1 and PD-L1, killer T cells are inhibited and thus unable to eliminate cancer cells (see figure). Antibody against PD-1 or PD-L1 can block direct interaction of these molecules. This releases the brake against killer T cells, and through re-activation, their ability to attack cancer cells is regained.

■ Immunotherapy through antibody blockade of the PD-1/PD-L1 immune checkpoint pathway

This method of targeting immune cells is a novel approach to cancer therapy, contrasting with the earlier therapies that directly target cancer cells. Moreover, this approach has been found to be extremely effective even in advanced forms of cancer. As such, regulating the immune system by targeting PD-1 and PD-L1 has attracted wide attention as a novel form of cancer immunotherapy, and various types of cancer are now being treated through the activation of our body’s immune system.

However, immune checkpoint inhibitors, including PD-1/PD-L1 blocking antibodies, are effective only in about 20 to 30 percent of patients. In addition, occurrences of autoimmune diseases have been reported as adverse events of checkpoint inhibition. It is believed that releasing the immune system’s brakes can trigger excessive immune responses, leading to such events (immune-related adverse events).

The CCII aims to further develop cancer therapy through research in identifying biomarkers to predict the effects of checkpoint blockade immunotherapy and occurrence of immune-related adverse events, as well as search for substances to enhance the effects of immunotherapy.