Immune checkpoints are inhibitory regulators of the immune system that are crucial to maintaining self-tolerance, preventing autoimmunity, and controlling the duration and extent of immune responses in order to minimize collateral tissue damage. These immune checkpoints are often overexpressed on tumor cells or on non-transformed cells within the tumor microenvironment, and compromise the ability of the immune system to mount an effective anti-tumor response.

Immune responses are regulated by a balance between co-stimulatory and inhibitory signaling pathways, which are stimulated by an assortment of receptors and their respective ligands (Figure 1). The ability to shift the balance towards a desired response can offer a way to ameliorate a variety of diseases.

The blockade of immune checkpoints is among the current most promising approaches for activating therapeutic antitumor immunity and circumventing the immune resistance exhibited by many tumors. The first immune checkpoint therapy approved by the FDA targeted the Cytotoxic T-lymphocyte associated antigen 4 (CTLA4) pathway (Ipilimumab, trade name Yervoy, Bristol-Myers Squibb). Subsequently, the FDA approved two treatments targeting the programmed cell death protein 1 (PD-1) pathway.

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