Precipitation of Autoimmune Diabetes With Anti-PD-1 Immunotherapy

Immunotherapy targeting T-cell regulatory molecules is highly effective in multiple cancers refractory to standard chemotherapies. However, blocking inhibitory molecules on activated T cells not only increases tumor cell destruction but also can breach tolerance, enabling pathological T cells to react with self-antigens. Indeed, autoimmune endocrinopathies, including hypophysitis, hypopituitarism, and thyroiditis, have been reported in trials involving anti-CTLA-4 and anti-PD-1 monoclonal antibodies (1–3). But autoimmune diabetes has not been definitively linked to these agents. We describe the development of new-onset insulin-dependent diabetes in five patients after receiving anti-PD-1 antibodies, either as single agent or in combination with other cancer drugs. Clinical history and key laboratory findings are summarized in Table 1. Notably, while the patients presented with diverse cancer types, and some had been treated with other immunological agents, their …