Immune Checkpoint Proteins

The immune checkpoint (ICP) molecules refer to ligand-receptor pairs that exert inhibitory or stimulatory effect on immune responses. Most of the ICP proteins that have been described are expressed on cells of the adaptive immune system, particularly on T cells, and of the innate immune system. ICP proteins act as important immune regulators in maintaining immune homeostasis and preventing autoimmunity. Some cancer cells can bind co-inhibitory receptor molecules to limit normal anti-tumor immune responses, thus assisting in immune escape. ICP therapy for cancer encompasses strategies that target these regulatory pathways to reinvigorate the anti-tumor function of immune cells. A number of inhibitory immunoreceptors have been identified and studied in cancer in past decades, including but not limited to PD-1, CTLA-4, LAG3, TIM3, TIGIT and BTLA. The most successful immune checkpoint blockade therapy is anti-PD-1/PD-L1 therapy that has been approved to treat a wide variety of cancer types, such as blood, skin, lung, liver, bladder and kidney cancers.

Common inhibitory and stimulatory immune checkpoint pathways