A narrative review of immune checkpoint mechanisms and current immune checkpoint therapy
Siqi Peng, Yifeng Bao
Abstract
Abstract: In recent decades, the unique advantages of immunotherapy have led to it playing a pivotal role in clinical and scientific research. Immune checkpoints as the key regulatory molecules of immune activation are critical to the function of the immune system. Many foreign invaders, such as cancer cells and other pathogens, overactivated immune checkpoints to escape capture by the immune system. Immune checkpoint therapy has been developed to counter this overactivation, and has achieved considerable clinical success. Cytotoxic T lymphocyte-associated antigen-4 and programmed cell death protein 1 are the two most well-known receptors that downregulate immune responses, and the scientists that discovered these molecules were awarded the 2018 Nobel Prize in Physiology or Medicine. Many other immune checkpoints have been described, such as lymphocyte-activation gene 3, T cell immunoglobulin and mucin domain 3, T-cell immunoreceptor with immunoglobulin and ITIM domain, tumour necrosis factor receptor 2, 4-1BB, CD27 and inducible T-cell co-stimulator (ICOS). Some monoclonal antibodies that target immune checkpoints have led to significant clinical responses, but they have limited monotherapeutic efficacy. Combination therapy may thus provide more effective treatment. In this review, we summarise the mechanisms of the major immune checkpoint molecules and the application of selected immune checkpoint inhibitors in clinical cancer therapy. Finally, we briefly discuss the future application and development of immunotherapies that target immune checkpoints.