Cancer immunotherapy by targeting immune checkpoints: Mechanism of T cell dysfunction in cancer immunity and new therapeutic targets John T Kung

Immune checkpoints or coinhibitory receptors,such as cytotoxic t lymphocyte antigen (ctla)-4 and programmed death (pd)-1,play important roles in regulating t cell responses,and they were proven to be effective targets in treating cancer. in chronic viral infections and cancer,t cells are chronically exposed to persistent antigen stimulation. this is often associated with deterioration of t cell function with constitutive activation of immune checkpoints,a state called 'exhaustion',which is commonly associated with inefficient control of tumors and persistent viral infections. immune checkpoint blockade can reinvigorate dysfunctional/exhausted t cells by restoring immunity to eliminate cancer or virus-infected cells. these immune checkpoint blocking antibodies have moved immunotherapy into a new era,and they represent paradigm-shifting therapeutic strategies for cancer treatment. a clearer understanding of the regulatory roles of these receptors and elucidation of the mechanisms of t cell dysfunction will provide more insights for rational design and development of cancer therapies that target immune checkpoints. this article reviews recent advance(s) in molecular understanding of t cell dysfunction in tumor microenvironments. in addition,we also discuss new immune checkpoint targets in cancer therapy. © 2017 the author(s).