Cancer immunotherapy and the PD-1/PD-L1 checkpoint pathway

Abstract

Long-term survival for patients with advanced bladder cancer is precarious, with a 5-year survival of just 5% in metastatic cases. Normally, the binding of PD-L1 to PD-1 alters the immune activity by modulating it to inhibit autoimmune diseases or chronic inflammation. However, some cancers use this route to block the immune response of the patient and continue growing. The new immunotherapy against bladder cancer aims to block the ability of tumor cells to resist patient' immune response by acting on the checkpoints of immune cells. These drugs are able to block the PD-1 receptor present on the surface of the lymphocytes, or the PD-L1 and PD-L2 ligands expressed by the cancer cells; this would prevent the binding of both blocking the immunomodulatory signal and allowing the T cells continue active against the tumor. The therapeutic target of Pembrolizumab and Nivolumab is PD-1, the receptor protein of PD-L1 in immune cells. The rest of molecules approved for different types of cancer such as Atezolizumab, Avelumab or Durvalumab act on the PD-L1 protein that is expressed in high concentrations in some cancer cells. The checkpoint inhibitors offer an effective alternative for patients for whom previously there were few options for durable responses, including those who are ineligible for cisplatin-based regimens or who are at risk of significant toxicity. This review describes the most recent data on agents that inhibit PD-L1, found on the surface of tumor cells, and PD-1 found on activated T and B cells and macrophages. Research is ongoing to further categorize responses, define ideal patient populations, and investigate combinations of checkpoint inhibitors to address multiple pathways in the functioning immune system.