The immunocheckpoints in modern oncology: the next 15 years

The notion that the immune system can act as a key factor in controlling cancer cell proliferation and thus its stimulation may be an important resource for cancer therapy has long been known. Tumors can elude the immune system by deploying proteins that shut down the immune response by binding to specific surface receptors on immune cells. Several promising strategies have been designed to overcome cancer cells' ability to suppress the immune surveillance. Immune checkpoint molecules that block cytotoxic T-lymphocyte associated antigen-4 (ipilimumab) or the programmed death-1/programmed death-ligand 1 axis (i.e., nivolumab and pembrolizumab) promote antitumor immunity, reactivating T-cell proliferation and activity. This efficient strategy currently represents one of the major oncological breakthroughs, with impressive clinically durable responses observed in cancer patients, particularly in melanoma, renal cell carcinoma, NSCLC and more recently in bladder cancer patients. Fifteen years ago, we replaced the IL-2 and INF-α for molecular targeted therapies. Today, we believe that immune therapy will represent the future, perhaps as part of a combination of different therapeutic strategies that act synergistically in each tumor and individual patient.