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Journal of Biomedical Science

, 24:35

Immunotherapy against cancer and immune disorders


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 advances in molecular understanding of T cell dysfunction in tumor microenvironments. In addition, we also discuss new immune checkpoint targets in cancer therapy.

KeywordsCancer immunotherapy Immune checkpoint T cell exhaustion New therapeutic targets AbbreviationsAPCAntigen presenting cells

CTLA-4Cytotoxic T lymphocytes antigen- 4

DCDendritic cell

EAEExperimental autoimmune encephalomyelitis

HBVHepatitis B virus

HCVHepatitis C virus

HIVHuman immunodeficiency virus


LAG-3Lymphocyte activation gene 3 protein

MDSCMyeloid-derived suppressor cells

MHCMajor histocompatibility complex

NK cellNatural killer cell

PD-1Programmed death-1

TCRT-cell receptor

TIGITT cell immunoglobulin and ITIM domain

TILTumor infiltrating lymphocyte

Tim-3T cell immunoglobulin- and mucin-containing molecule-3

TregRegulatory T cells

Autor: Hwei-Fang Tsai - Ping-Ning Hsu


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