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Checkpoint inhibitors have an anticancer effect by removing a negative regulatory signal for T-cell activation from the tumor microenvironment (Fig. 1). They include cytotoxic T-cell–associated antigen (CTLA-4), programmed cell death protein-1 (PD-1), and programmed cell death ligand-1 (PDL-1) antibodies and are now being widely used for the treatment of different types of cancer. From the initial phases of checkpoint inhibitor use, there has been concern about the potential for the development of autoimmune disease as a result of T-cell activation. Subsequently, multiple autoimmune diseases were indeed observed as a result of these medications (1). Although both PD-1 and PDL-1 antibodies can precipitate type 1 diabetes in the nonobese diabetic mice model (2), only very recent reports have noted type 1 diabetes after PD-1 antibody use in humans (3,4). Here, we describe two older adults without diabetes receiving agents inhibiting the PD-1 pathway for resistant cancers who developed acute type 1 diabetes.
Via Krishan Maggon
+Author Affiliations
1Division of Metabolism, Endocrinology and Nutrition, University of Washington, Seattle, WA2Division of Medical Oncology, University of Washington, Seattle, WA3Division of Endocrinology, VA Puget Sound Health Care System, Seattle, WA4Pacific Northwest Diabetes Research Institute, Seattle, WACorresponding author: Irl B. Hirsch, ihirsch@uw.edu.Published online before printJune 26, 2015, doi:10.2337/dc15-0889Diabetes Care September 2015vol. 38 no. 9 e137-e138Anti–PD-1 and Anti–PDL-1 Monoclonal Antibodies Causing Type 1 DiabetesMahnaz Mellati1, Keith D. Eaton2, Barbara M. Brooks-Worrell1,3,William A. Hagopian1,4, Renato Martins2, Jerry P. Palmer1,3 andIrl B. Hirsch1⇑
+Author Affiliations
1Division of Metabolism, Endocrinology and Nutrition, University of Washington, Seattle, WA2Division of Medical Oncology, University of Washington, Seattle, WA3Division of Endocrinology, VA Puget Sound Health Care System, Seattle, WA4Pacific Northwest Diabetes Research Institute, Seattle, WACorresponding author: Irl B. Hirsch, ihirsch@uw.edu.
Treatment of cancer requires boosting the immune system, while that of autoimmunity requires restraining it. Thus, cancer drugs that relieve some of the natural breaks of immune response could potentially induce or aggravate autoimmune diseases. Here, we have evidence that biologics blocking the PD1/PDL1 pathway is associated with the development of T1D.