However, tumor cells have evolved to ‘hijack’ this mechanism to escape from immunosurveillance. Some tumor cells express several different immune checkpoint proteins on their surface and secrete them into circulation. Once these immune checkpoint proteins bind to the cognate receptors on our T cells, the function of T cells will be impaired. As a result, our immune system subsequently loses the ability to kill the tumor cells due to the inability to recognize the cancer cells.
After delineating this mechanism, scientists have developed several drugs targeting the pathway. These types of immunotherapy are called immune checkpoint inhibitors. One of the functions that modern cancer drugs target is the PD-L1/PD-1 interaction. This type of immunotherapy works by blocking the immune checkpoint proteins on cancer cells, therefore restoring our immune cells’ ability to identify and eradicate the tumor. Common FDA approved drugs targeting PD-L1 include Atezolizumab, Avelumab and Durvalumab. Another set of drugs targeting PD-1 are Nivolumab and Pembrolizumab. Recently, the combined effects of immune checkpoint inhibitors together with other chemotherapy or radiotherapy have been studied. The results show that if some of the tumor cells are initially killed by cytotoxic therapy (i.e. through chemotherapy or radiotherapy), this enhances the effects of immune checkpoint inhibitors. Due to these positive findings, studies focusing on modulating the immune system to fight against cancer continue to be performed today.