PD-1/PD-L1 immunotherapy blockade in solid tumors: role of PD-1/PD-L1 in cancer disease progression

This literature review summarizes the biological concept behind cancer and focuses on the use of PD-1 in tumors as a way of immune evasion as well as the use of PD-1/PD-L1 blockade as an innovative target for immunotherapy. Cancer arises from mutagenic events resulting in the presence of abnormal cells and uncontrollable cell proliferation. It is able to evade immune activity through many methods of immune evasion, one of which is the PD-1/PD-L1 blockade. Normally PD-1 binds to PD-L1 to dampen the immune response after activation and cancer is able to take advantage of this immune homeostasis pathway to prevent immune attack. It has been shown that inhibition of the PD-1/PD-L1 blockade can act to block the interaction between PD-1 and PD-L1, thus allowing the T cells of the immune system to activate and attack the cancer. This has led to the invention of PD-1/PD-L1 checkpoint inhibitors, with currently 6 approved by the FDA for the treatment of a wide spectrum of cancers. The discovery of PD-1/PD-L1 blockade has made a leap of advancements in cancer immunotherapy; however, as the number of therapies is expected to rise in the future, several issues remain that require further investigation to optimize the potential of PD-1/PD-L1 inhibitors. Specifically, mechanisms of resistance, mechanisms behind non-immunogenic tumors, and immune-related adverse events are areas that warrant further examination in order to fully maximize the benefits and minimize the risks of PD-1/PD-L1 inhibitors. The bispecific combination molecule cotargeting PD-1/PD-L1 could be a possible alternative therapeutic approach with enhanced antitumor activity compared to the traditional monoclonal PD-1 or PD-L1 inhibitors