Emerging Concepts Targeting Immune Checkpoints in Cancer and Autoimmunity PDF
|Author||Akihiko Yoshimura and Akihiko Yoshimura|
|File size||5.25 MB|
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The homeostasis of the immune system is maintained by positive and negative factors including effector/regulatory cells as well as positive intracellular signals/negative regulators. Autoimmune diseases and allergic diseases are states in which this balance inclines to the excessive “positive.” In contrast, tumor microenvironment provides negative signals for immune systems, which suppress anti-tumor immunity. Those include regulatory T cells (Tregs) and myeloid-derived suppressor cell (MDSC) as well as immune regulatory molecules such as PD-L1, indoleamine 2,3-dioxygenase (IDO), TGF-b. Autoimmunity and anti-tumor immunity are two sides of the same coin. Indeed, knockout mice of various molecules so-called “immune checkpoints” often develop autoimmune diseases.
Thus, the understanding of the mechanism of immunological balance is important for the treatment of both autoimmune diseases and cancer. Typical positive and negative T cells of immune balance are effector T cells and regulatory T cells (Tregs), respectively. Major Treg cells developed in the thymus are called thymus-derived Treg (tTreg) cells. Treg cells are specified by an expression of the transcription factor Forkhead box P3 (Foxp3), which plays crucial roles in the differentiation, maintenance, and function of tTreg cells. Treg cells are believed to be involved in autoimmune diseases and allergy because Treg cells suppress excess immunity against a diverse range of antigens, including self-antigens, commensal bacteria-derived antigens, and environmental allergens. Tregs have been shown to be abundant in tumor tissues and suppress anti-tumor immunity.
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