Immune-related adverse events of checkpoint inhibitors: Insights into immunological dysregulation

Yang, Huaxia; Yao, Zhuoran; Zhou, Xiaoxiang; Zhang, Wen; Zhang, Xuan; Zhang, Fengchun

doi:10.1016/j.clim.2020.108377

Cited by 52 publications

(73 citation statements)

References 125 publications

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“…18 Finally, regulatory T (Treg) cell depletion has been suggested to play a role in the development of irAEs, as Treg cells are essential for maintaining peripheral tolerance. 19 CTLA-4 is constitutively expressed on Treg cells while PD-1 expression is restricted to subpopulations. CTLA-4 blockade can affect Treg cell number and function; reduced Treg cell number and increased effector T cells to Treg cells ratio have been observed in patients treated with ipilimumab.…”

Section: General Mechanism Of Action Underlying Ici Toxicitymentioning

confidence: 99%

Liver toxicity as a limiting factor to the increasing use of immune checkpoint inhibitors

et al. 2020

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Immune checkpoint inhibitors (ICIs) improve clinical outcomes in patients suffering from different types of cancer. Liver toxicity is one of the immune-related adverse events associated with immunotherapy; although not common, its management is challenging as it is extremely heterogeneous in terms of presentation and severity. Differences in the development and evolution of ICI-related toxicity in healthy or cirrhotic livers have not yet been elucidated. Assessing causality is key to diagnosing ICI-induced liver toxicity; liver biopsies can assist not only in the differential diagnosis but also in assessing the severity of histological liver damage. The current classification of severity overestimates the grade of liver injury and needs to be revised to reflect the views of hepatologists. Spontaneous improvements in ICI-related liver toxicity have been reported, so corticosteroid therapy should probably be individualised not systematic. The reintroduction of ICIs in a patient with previous immune-mediated hepatitis may be possible, but the risk/benefit ratio should be considered, as the risk factors for hepatitis recurrence are currently unclear. The management of these patients, requiring a balance between efficacy, toxicity and specific treatments, necessitates multidisciplinary collaboration. The incidence of immune-related liver toxicity will continue to rise based on the increasing use of ICIs for most cancers, mandating improved understanding and management of this complication.

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Section: General Mechanism Of Action Underlying Ici Toxicitymentioning

confidence: 99%

Liver toxicity as a limiting factor to the increasing use of immune checkpoint inhibitors

et al. 2020

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“…The irAEs are autoimmune complications of check-point inhibitors (CPI) therapy used in cancer treatment. The main difference of IrAEs in comparison with AID is a lack of the chronicity [ 103 ]. It is one of the ASIA classical example where the external stimuli are known, and its pathogenesis is well described.…”

Section: Classical Examples Of the Asia Syndromementioning

confidence: 99%

Classical Examples of the Concept of the ASIA Syndrome

et al. 2020

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Autoimmune/inflammatory syndrome induced by adjuvants (ASIA) was first introduced in 2011 by Shoenfeld et al. and encompasses a cluster of related immune mediated diseases, which develop among genetically prone individuals as a result of adjuvant agent exposure. Since the recognition of ASIA syndrome, more than 4400 documented cases have been reported so far, illustrated by heterogeneous clinical manifestations and severity. In this review, five enigmatic conditions, including sarcoidosis, Sjögren’s syndrome, undifferentiated connective tissue disease, silicone implant incompatibility syndrome (SIIS), and immune-related adverse events (irAEs), are defined as classical examples of ASIA. Certainly, these disorders have been described after an adjuvant stimulus (silicone implantation, drugs, infections, metals, vaccines, etc.) among genetically predisposed individuals (mainly the HLA-DRB1 and PTPN22 gene), which induce an hyperstimulation of the immune system resulting in the production of autoantibodies, eventually leading to the development of autoimmune diseases. Circulating autonomic autoantibodies in the sera of patients with silicone breast implants, as well as anatomopathological aspects of small fiber neuropathy in their skin biopsies have been recently described. To our knowledge, these novel insights serve as a common explanation to the non-specific clinical manifestations reported in patients with ASIA, leading to the redefinition of the ASIA syndrome diagnostic criteria.

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“…Immune checkpoint inhibitors (ICPIs) are an effective treatment for advanced malignancies. They work by releasing the brake that has been placed on the immune system, allowing the patients' immune system to attack cancer cells, but also certain healthy tissues [1][2][3]. The primary targets for checkpoint inhibition include programmed cell death receptor 1 (PD1), programmed cell death ligand 1 (PD-L1), and cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4).…”

Section: Introductionmentioning

confidence: 99%

“…The primary targets for checkpoint inhibition include programmed cell death receptor 1 (PD1), programmed cell death ligand 1 (PD-L1), and cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4). Antibodies inhibiting PD-1 (pembrolizumab, nivolumab) and PD-L1 (atezolizumab, avelumab, durvalumab) have been approved for treatment in several types of cancer, including melanoma of the skin, non-small cell lung cancer, kidney cancer, bladder cancer, head and neck cancers, and Hodgkin lymphoma [1][2][3]. As their use increases, their side effects have become more prevalent.…”

Section: Introductionmentioning

confidence: 99%

Immune Checkpoint Inhibitor-Induced Acute Pancreatitis and Colitis

Pagan

Arroyo-Martinez

Tandon

et al. 2020

Cureus

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Given the promising response of immune checkpoint inhibitors (ICPIs) in treating advanced malignancies, their use in clinical practice is on the rise. ICPIs are associated with a wide spectrum of immune-related adverse events (irAEs). The reported side effects of therapy can be severe enough to require interruption or withdrawal. We are presenting a case of a checkpoint inhibitor-induced acute pancreatitis and colitis, treated with high-dose steroids. This case highlights the need for all physicians to be aware of the different presentations of irAEs from checkpoint inhibitors to provide the correct diagnosis and management.

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Immune-related adverse events of checkpoint inhibitors: Insights into immunological dysregulation

Cited by 52 publications

References 125 publications

Liver toxicity as a limiting factor to the increasing use of immune checkpoint inhibitors

Liver toxicity as a limiting factor to the increasing use of immune checkpoint inhibitors

Classical Examples of the Concept of the ASIA Syndrome

Immune Checkpoint Inhibitor-Induced Acute Pancreatitis and Colitis

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