Cancer immunotherapy by targeting immune checkpoints: Mechanism of T cell dysfunction in cancer immunity and new therapeutic targets John T Kung
Journal
Journal of Biomedical Science
Journal Volume
24
Journal Issue
1
Date Issued
2017
Author(s)
Tsai H.-F.
Abstract
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).
Subjects
Cancer immunotherapy; Immune checkpoint; New therapeutic targets; T cell exhaustion
SDGs
Other Subjects
cytotoxic T lymphocyte antigen 4; hepatitis A virus cellular receptor 2; immune checkpoint; immunoglobulin receptor; LAG 3 protein; membrane protein; programmed death 1 ligand 1; T lymphocyte receptor; TIGIT protein; unclassified drug; autoimmunity; cancer immunotherapy; CD8+ T lymphocyte; effector cell; human; immune response; immunocompetent cell; immunoregulation; malignant neoplasm; nonhuman; priority journal; Review; T lymphocyte; tumor immunity; tumor microenvironment; virus infection; animal; cell cycle checkpoint; immunology; immunotherapy; mouse; neoplasm; T lymphocyte; Animals; Cell Cycle Checkpoints; Humans; Immunotherapy; Mice; Neoplasms; T-Lymphocytes; Tumor Microenvironment
Publisher
BioMed Central Ltd.
Type
review