Checkpoint blockade for cancer therapy: revitalizing a suppressed immune system

• Immune checkpoints dampen T cell activation, avoiding excessive immune responses.
• CTLA-4 and PD-1 are currently the two most clinically relevant immune checkpoints.
• Checkpoint blockade acts by activating the immune system to eliminate tumors.
• Checkpoint-blockade therapies have shown impressive increases in overall survival.

Immune checkpoint receptors are crucial molecules for fine-tuning immune responses. Checkpoint signaling dampens T cell activation to avoid autoimmunity and the destructive effects of an excessive inflammatory response. It is well established that tumors use several mechanisms to avoid elimination by the immune system, and one involves hijacking these checkpoint pathways. Checkpoint blockade therapy utilizes monoclonal antibodies to release the brakes from suppressed T cells, allowing them to be activated and recover their antitumor activity. This therapeutic approach has revolutionized cancer immunotherapy, and extraordinary increases in overall survival were noted, first with anti-CTLA-4 (cytotoxic T lymphocyte-associated protein 4) and subsequently with anti-PD-1 (programmed cell death receptor-1) in melanoma and other malignancies.