Unravelling Checkpoint Inhibitor Associated Autoimmune Diabetes: From Bench to Bedside

Linda Wu; Venessa H M Tsang; Sarah C Sasson; Alexander M Menzies; Matteo S Carlino; David A Brown; Roderick Clifton-Bligh; Jenny E Gunton

doi:10.3389/fendo.2021.764138

Unravelling Checkpoint Inhibitor Associated Autoimmune Diabetes: From Bench to Bedside

Front Endocrinol (Lausanne). 2021 Nov 5:12:764138. doi: 10.3389/fendo.2021.764138. eCollection 2021.

Authors

Linda Wu^{1

2

3

4}, Venessa H M Tsang^{2

4}, Sarah C Sasson^{4

5

6}, Alexander M Menzies^{4

7

8}, Matteo S Carlino^{4

8

9}, David A Brown^{1

4

5

6}, Roderick Clifton-Bligh^{2

4}, Jenny E Gunton^{1

3

4}

Affiliations

¹ Centre for Diabetes, Obesity and Endocrinology, The Westmead Institute for Medical Research, Sydney, NSW, Australia.
² Department of Endocrinology, Royal North Shore Hospital, Sydney, NSW, Australia.
³ Department of Endocrinology, Westmead Hospital, Sydney, NSW, Australia.
⁴ Faculty of Medicine and Health, The University of Sydney, Sydney, NSW, Australia.
⁵ Department of Immunology, Westmead Hospital, Sydney, NSW, Australia.
⁶ NSW Health Pathology, Institute of Clinical Pathology and Medical Research (ICPMR), Sydney, NSW, Australia.
⁷ Department of Medical Oncology, Royal North Shore Hospital, Sydney, NSW, Australia.
⁸ Melanoma Institute Australia, The University of Sydney, Sydney, NSW, Australia.
⁹ Department of Medical Oncology, Westmead Hospital, Sydney, NSW, Australia.

Abstract

Immune checkpoint inhibitors have transformed the landscape of oncological therapy, but at the price of a new array of immune related adverse events. Among these is β-cell failure, leading to checkpoint inhibitor-related autoimmune diabetes (CIADM) which entails substantial long-term morbidity. As our understanding of this novel disease grows, parallels and differences between CIADM and classic type 1 diabetes (T1D) may provide insights into the development of diabetes and identify novel potential therapeutic strategies. In this review, we outline the knowledge across the disciplines of endocrinology, oncology and immunology regarding the pathogenesis of CIADM and identify possible management strategies.

Keywords: diabetes mellitus; immune checkpoint inhibitor (ICI); immune related adverse events; immunotherapy; type 1 diabetes.

Publication types

Research Support, Non-U.S. Gov't
Review

MeSH terms

Antineoplastic Agents, Immunological / adverse effects
Antineoplastic Agents, Immunological / immunology
Diabetes Mellitus, Type 1 / blood*
Diabetes Mellitus, Type 1 / chemically induced*
Diabetes Mellitus, Type 1 / drug therapy
Diabetes Mellitus, Type 1 / immunology
Humans
Hyperglycemia / blood
Hyperglycemia / chemically induced
Hyperglycemia / drug therapy
Hyperglycemia / immunology
Immune Checkpoint Inhibitors / adverse effects*
Immune Checkpoint Inhibitors / immunology
Insulin / blood
Insulin / immunology
Insulin / therapeutic use
Risk Factors

Substances

Antineoplastic Agents, Immunological
Immune Checkpoint Inhibitors
Insulin