APS Type 1 research has long been seen as a bridge to gaining insights into the treatment of many other autoimmune disorders, and as this article makes clear, may also help provide a bridge into gaining insights the treatment of cancer.

TitleAutoimmunity and Cancer – Two sides of the Same Coin
AuthorsJustyna Sakowska, Lukasz Arcimowicz, Martyna Jankowiak, Ines Papak, Aleksandra Markiewicz, Katarzyna Dziubek, Malgorzata Kurkowiak, Sachin Kote, Karolina Kazmierczak-Siedlecka, Karol Polom, Natalia Marek-Trzonkowska, and Piotr Trzonkowski
PublicationFrontiers in Immunity, 13 May 2022
Dave’s DescriptionFailure or breakdown of self-tolerance leads to autoimmunity and autoimmune disease.  Tolerance is classified into central tolerance and peripheral tolerance.  Central tolerance is the main way the immune system learns to discriminate self from non-self. We have now come to appreciate that AIRE (the autoimmune regulator gene responsible for APS Type 1) plays a key role in the development of central tolerance. Because of this, there has been worldwide interest in research that seeks to understand AIRE through the study of APS Type Type 1. This research has long been seen as a bridge to gaining insights into the treatment of many other autoimmune disorders. This article makes clear may also help provide a bridge to gaining insights into the treatment of cancer.
Key quotes“The hallmark of autoimmunity is the presence of autoreactive T and B cells that were not deleted by the mechanisms of central tolerance. One of the most studied defects of T-cell-negative selection is mutations in the transcriptional autoimmune regulator gene (AIRE) (emphasis added). AIRE is mainly expressed by the thymic medullary epithelial cells (mTECs) and is responsible for the expression of tissue-restricted antigens within the thymus. The T cells responding to these antigens are considered self-reactive and eliminated through negative selection. Thus, when AIRE is defective, the T cells specific to self-antigens leave the thymus and enter circulation. This results in a variety of autoimmune disorders. The mouse models of Aire knockout showed that the AIRE expression prevents multiorgan lymphocyte infiltration, various organ-specific autoantibodies, and infertility. In humans, AIRE mutations lead to a severe condition called autoimmune polyendocrinopathy syndrome type 1 (APS1) (emphasis added).”

“Autoimmune disease results from the immune response against self-antigens, while cancer develops when the immune system does not respond to malignant cells. Thus, for years, autoimmunity and cancer have been considered as two separate fields of research that do not have a lot in common. However, the discovery of immune checkpoints and the development of anti-cancer drugs targeting PD-1 (programmed cell death receptor 1) and CTLA-4 (cytotoxic T lymphocyte antigen 4) pathways proved that studying autoimmune diseases can be extremely helpful in the development of novel anti-cancer drugs. Therefore, autoimmunity and cancer seem to be just two sides of the same coin (emphasis added).

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