Immune checkpoints are important immune regulators in maintaining immune homeostasis and preventing autoimmunity. These consist of both stimulatory and inhibitory pathways that are important for maintaining self-tolerance and regulating the type, magnitude, and duration of the immune response. Nevertheless, in cancer, the expression of immune checkpoints often dysregulates, and these pathways are activated to inhibit the anti-tumor immune responses. Therefore, changing the balance of the immune system via immune checkpoint therapies should allow it to be fully activated to detect and eliminate cancer. The most widely studied and recognized checkpoints are the inhibitory pathways consisting of CTLA-4, PD-1, and PD-L1. Many biological agents that target these molecules are now broadly used in a variety of malignancies.
Immune Checkpoint Therapy in Cancers
In the last decade, significant advances have been made in cancer immunotherapy, such as immune checkpoint therapy. As a therapeutic class, drugs that inhibit these signaling pathways, also known as immune checkpoint inhibitors (ICIs), are currently utilized for a wide variety of malignancies and have demonstrated durable clinical activities in a subset of cancer patients. Some ICIs have been approved by the US Food and Drug Administration (FDA) for the treatment of a variety of cancers. Clinical trials are paving the way for new ICI therapy agents and expanding the current use of approved therapies.
In other aspects, several attempts of the development of agonistic antibodies against costimulatory receptors (ICOS, GITR, 4-1BB, etc.) have been made to stimulate anti-tumor activity and/or to eliminate immune-threatening suppressors. Moreover, new approaches and combination therapies are under development to broaden the clinical impact of immune checkpoint blockade by overcoming resistance to treatment and limiting adverse events.