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Immune checkpoint therapy and type 1 diabetes

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Abstract

Type 1 diabetes is caused by destruction of insulin-producing beta cells of the pancreas. The etiology of type 1 diabetes is immune-mediated by either an organ-specific autoimmune mechanism in autoimmune type 1 diabetes or a still unknown but probably immune-mediated mechanism in fulminant type 1 diabetes. Immunomodulation is therefore expected to accelerate or inhibit type 1 diabetes. Recent progress in anti-cancer therapy by immune-checkpoint blockade, such as anti-PD-1 and anti-CTLA4 monoclonal antibodies, has markedly improved the prognosis of patients with advanced cancers. These drugs activate anti-tumor immunity by blocking inhibitory signals of T lymphocytes. Activation of immunological pathways, however, is expected to accelerate immune-mediated diseases. In fact, the development of autoimmune-thyroid diseases and type 1 diabetes, including fulminant type 1 diabetes, has been reported in patients treated with immune checkpoint blockers. The development of fulminant type 1 diabetes is a major concern because of its abrupt onset and very rapid progression, leading to death unless proper treatment is initiated immediately after diagnosis. In this review, the development of type 1 diabetes with immune-checkpoint therapy and its etiological background are discussed.

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Acknowledgments

This study was supported by grants-in-aid for scientific research from Japan Society for the Promotion of Science (15K09404 to HI, 26461348 to YK, 26461349 to SN), a grant from the Ministry of Health, Labor and Welfare (H28-Jyunkanto-ippan-006 to HI) and a grant from Japan Agency for Medical Research and Development (16768653 to HI).

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Authors and Affiliations

  1. Department of Endocrinology, Metabolism and Diabetes, Kindai University Faculty of Medicine, 377-2 Ohno-higashi, Osaka-sayama, Osaka, 589-8511, Japan

    Hiroshi Ikegami, Yumiko Kawabata & Shinsuke Noso

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  1. Hiroshi Ikegami
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  2. Yumiko Kawabata
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  3. Shinsuke Noso
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Correspondence to Hiroshi Ikegami.

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This article dose not contain any studies with human or animal subjects performed by any of the authors.

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Ikegami, H., Kawabata, Y. & Noso, S. Immune checkpoint therapy and type 1 diabetes. Diabetol Int 7, 221–227 (2016). https://doi.org/10.1007/s13340-016-0276-9

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  • DOI: https://doi.org/10.1007/s13340-016-0276-9

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