Immune checkpoint blockade
Duda, Dan G. Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts.
- Cytotoxic T cells
- T-cell activation
- Immune checkpoints in cancer
- Immune checkpoint blockade to treat cancer
- Challenges and future directions
- Links to Primary Literature
- Additional Readings
A group of inhibitory pathways in immune cells that maintain self-tolerance and modulate T-cell immune responses to avoid tissue damage and autoimmunity. The physiologic function of immune checkpoints is to provide coinhibitory signals to the effector T cells (thymus-derived lymphocytes), counteract the costimulatory signals, and avoid autoimmunity and the destructive effects of excessive inflammatory responses. They are particularly important for the resolution phase of wound healing, and it has been demonstrated clinically that they may also play key roles in pathology. Many malignant tumors use at least some of the immune checkpoints [for example, programmed cell death 1 protein (PD-1) and cytotoxic T lymphocyte antigen 4 (CTLA-4)] to successfully evade the host immune system and grow and spread throughout the body. Discovery of this mechanism opened new avenues for the therapy of cancer using immune checkpoint blockade, which has dramatically changed the landscape of oncology in a period of only a few years. See also: Autoimmunity; Cancer; Cellular immunology; Immunity; Immunologic cytotoxicity; Immunology; Immunotherapy; Oncology; Tumor
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