Abstract
Immunotherapy is now a recognized treatment option for several types of cancer. However, some cancer patients treated with immune checkpoint inhibitors (ICIs) are subject to immune-related adverse events, including induced diabetes mellitus. The exact role and molecular/genetic action of ICIs in diabetes are still not well understood. Elucidating the underlying mechanisms in a proper fashion would allow better refining of biomarkers that would help diagnose patients at risk of altered immune system homeostasis, but would also hold the potential of new therapeutic options for diabetes. In the present narrative review, we propose to discuss the case of autoimmune diabetes following treatment with ICIs and the role of ICIs in the pathophysiology of diabetes. We also present some scarce available data on interesting potential immune therapies for diabetes.
Highlights
Battling cancer while having to deal with an ongoing autoimmune disease is a dilemma many cancer patients treated with immune checkpoint inhibitors (ICIs) face
As a matter of fact, the interaction of cytotoxic T-lymphocyte antigen-4 (CTLA-4), expressed on T-cells, with its ligands CD80 and CD86 plays a vital role in the downregulation of T-cell proliferation in early responses and T regulatory (Treg) cell function, whereas the interaction of programmed death-1 (PD-1), expressed on activated T-cells, with its ligands PD-L1 and PD-L2, limits the activity of effector T cells in peripheral tissues
In the case of malignancies, the balance is disrupted as some tumors expressing PD-L1 and PD-L2 interact with PD-1, promoting T-cell exhaustion associated with reduced proliferation, cytokine secretion and survival of effector T-cells, and enhancing the proliferation of Treg with the modulation of autoimmunity on the other hand [2]
Summary
Battling cancer while having to deal with an ongoing autoimmune disease is a dilemma many cancer patients treated with immune checkpoint inhibitors (ICIs) face. As immunotherapy increases the human body’s defenses, it is quite understandable to acknowledge its direct involvement in increasing the immune system’s mistakes. In the present narrative literature review, we will discuss the case of autoimmune diabetes following treatment with ICIs. Reviewing the available literature will allow us to gather insights into the role of immune checkpoints in the pathophysiology of type 1 diabetes mellitus (T1DM) and to propose a mechanism of pathogenesis for ICI-induced diabetes mellitus (ICIDM). We will present some scarce available data on the involvement of immune checkpoints in the pathophysiology of other types of diabetes, such as type 2 diabetes mellitus (T2DM), and interesting potential immune therapies for diabetes
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