Abstract
Immune checkpoint inhibitors (ICIs) such as anti-programmed death-1 (PD-1) and its ligand PD-L1 and anti-cytotoxic T-lymphocyte antigen 4 (CTLA-4) monoclonal antibodies, are involved in T cell-mediated immune response augmentation and promote anti-tumor immunity. Cancer patients treated with combination of immunotherapy, chemotherapy, radiotherapy, and targeted therapy exhibit superior clinical outcomes and tolerance compared with patients treated with monotherapies. However, immutherapy is associated with several concomitant immune-related adverse events (irAEs). For instance, IrAEs interferes with function of gastrointestinal tract, endocrine, dermatological, nervous system and musculoskeletal systems. ICIs-associated pancreatic injury might causes decrease in endocrine and exocrine pancreatic function, resulting in metabolic and nutritional disorders. Clinicians who administer immune checkpoint inhibitors to cancer patients are diagnosed with hyperglycemia, abdominal pain and steatorrhea. Currently, the precise mechanism of ICIs-associated pancreatic injury has not been fully explored. This paper summarizes incidence, diagnosis, clinical characteristics, potential mechanisms, and treatment management patterns of ICIs-associated pancreatic AEs based on previous studies. In addition, possible management approaches of these adverse effects are presented in this paper. in the findings summarized in this paper lay a basis for management of ICIs-associated pancreatic AEs and expanding future immunotherapy applications.
Highlights
Programmed death 1 (PD-1) receptors bind to programmed death-ligand 1 (PD-L1), transport negative signals to T cells, and regulate functions of effector T cells
The duration before onset of Immune checkpoint inhibitors (ICIs) associated with diabetes mellitus (ICIs-Type diabetes mellitus (DM)) is between 3 weeks and 81 weeks after immunotherapy initiation, and most cases are reported in patients without pre-existing T2DM [11, 25, 47, 68,69,70]
2 patients presented with positive autoantibodies [glutamic acid decarboxylase (GAD) and tyrosine-phosphatase inhibitor (IA2)] before anti-programmed death-1 (PD-1) treatment and diabetes onset
Summary
Programmed death 1 (PD-1) receptors bind to programmed death-ligand 1 (PD-L1), transport negative signals to T cells, and regulate functions of effector T cells. Use of immune checkpoint inhibitors (ICIs), including anti-PD-1 monoclonal antibodies (nivolumab and pembrolizumab), anti-PD-L1 monoclonal antibodies (atezolizumab, avelumab, and durvalumab), and anti-CTLA-4 monoclonal antibodies (ipilimumab and tremelimumab), triggers activation and expansion of T lymphocytes These inhibitors act by blocking inhibitory signals of T cells and enhancing ability of the immune system to fight cancer cells (Figure 1). The duration before onset of ICIs associated with diabetes mellitus (ICIs-DM) is between 3 weeks and 81 weeks after immunotherapy initiation, and most cases are reported in patients without pre-existing T2DM [11, 25, 47, 68,69,70]. 2 patients presented with positive autoantibodies [glutamic acid decarboxylase (GAD) and tyrosine-phosphatase inhibitor (IA2)] before anti-PD-1 treatment and diabetes onset. A few subjects exhibit pre-existing T2DM, which is effectively regulated without insulin These patients experience a sharp increase in blood glucose levels after treatment initiation with
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