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Immune-Related Adverse Events Due to Cancer Immunotherapy: Immune Mechanisms and Clinical Manifestations.

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Title: Immune-Related Adverse Events Due to Cancer Immunotherapy: Immune Mechanisms and Clinical Manifestations.
Authors: Casagrande, Silvia, Sopetto, Giulia Boscato, Bertalot, Giovanni, Bortolotti, Roberto, Racanelli, Vito, Caffo, Orazio, Giometto, Bruno, Berti, Alvise, Veccia, Antonello
Source: Cancers; Apr2024, Vol. 16 Issue 7, p1440, 30p
Subject Terms: RISK assessment, IMMUNOTHERAPY, PROGRAMMED death-ligand 1, IMMUNE checkpoint inhibitors, PROGRAMMED cell death 1 receptors, AUTOIMMUNE diseases, ADVERSE health care events, PHARMACODYNAMICS, DISEASE risk factors
Abstract: Simple Summary: This review comprehensively summarizes the pathogenic mechanisms responsible for immune-related Adverse Events (irAEs) arising from self-tolerance loss due to Immune Checkpoint Inhibitors (ICIs) and discusses the main clinical manifestations due to irAEs categorized by organ types, their incidence, and risk factors. In addition, it focuses on the different distributions in frequencies of the diverse clinical manifestations due to irAEs between CTLA4 and PD1 pathway inhibitors and the intricate differential with primary autoimmune disorders, which share some pathophysiological and clinical aspects. The landscape of cancer treatment has undergone a significant transformation with the introduction of Immune Checkpoint Inhibitors (ICIs). Patients undergoing these treatments often report prolonged clinical and radiological responses, albeit with a potential risk of developing immune-related adverse events (irAEs). Here, we reviewed and discussed the mechanisms of action of ICIs and their pivotal role in regulating the immune system to enhance the anti-tumor immune response. We scrutinized the intricate pathogenic mechanisms responsible for irAEs, arising from the evasion of self-tolerance checkpoints due to drug-induced immune modulation. We also summarized the main clinical manifestations due to irAEs categorized by organ types, detailing their incidence and associated risk factors. The occurrence of irAEs is more frequent when ICIs are combined; with neurological, cardiovascular, hematological, and rheumatic irAEs more commonly linked to PD1/PD-L1 inhibitors and cutaneous and gastrointestinal irAEs more prevalent with CTLA4 inhibitors. Due to the often-nonspecific signs and symptoms, the diagnosis of irAEs (especially for those rare ones) can be challenging. The differential with primary autoimmune disorders becomes sometimes intricate, given the clinical and pathophysiological similarities. In conclusion, considering the escalating use of ICIs, this area of research necessitates additional clinical studies and practical insights, especially the development of biomarkers for predicting immune toxicities. In addition, there is a need for heightened education for both clinicians and patients to enhance understanding and awareness. [ABSTRACT FROM AUTHOR]
Copyright of Cancers is the property of MDPI and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
Database: Complementary Index
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  Data: Immune-Related Adverse Events Due to Cancer Immunotherapy: Immune Mechanisms and Clinical Manifestations.
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  Data: <searchLink fieldCode="AR" term="%22Casagrande%2C+Silvia%22">Casagrande, Silvia</searchLink><br /><searchLink fieldCode="AR" term="%22Sopetto%2C+Giulia+Boscato%22">Sopetto, Giulia Boscato</searchLink><br /><searchLink fieldCode="AR" term="%22Bertalot%2C+Giovanni%22">Bertalot, Giovanni</searchLink><br /><searchLink fieldCode="AR" term="%22Bortolotti%2C+Roberto%22">Bortolotti, Roberto</searchLink><br /><searchLink fieldCode="AR" term="%22Racanelli%2C+Vito%22">Racanelli, Vito</searchLink><br /><searchLink fieldCode="AR" term="%22Caffo%2C+Orazio%22">Caffo, Orazio</searchLink><br /><searchLink fieldCode="AR" term="%22Giometto%2C+Bruno%22">Giometto, Bruno</searchLink><br /><searchLink fieldCode="AR" term="%22Berti%2C+Alvise%22">Berti, Alvise</searchLink><br /><searchLink fieldCode="AR" term="%22Veccia%2C+Antonello%22">Veccia, Antonello</searchLink>
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  Data: Cancers; Apr2024, Vol. 16 Issue 7, p1440, 30p
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  Data: <searchLink fieldCode="DE" term="%22RISK+assessment%22">RISK assessment</searchLink><br /><searchLink fieldCode="DE" term="%22IMMUNOTHERAPY%22">IMMUNOTHERAPY</searchLink><br /><searchLink fieldCode="DE" term="%22PROGRAMMED+death-ligand+1%22">PROGRAMMED death-ligand 1</searchLink><br /><searchLink fieldCode="DE" term="%22IMMUNE+checkpoint+inhibitors%22">IMMUNE checkpoint inhibitors</searchLink><br /><searchLink fieldCode="DE" term="%22PROGRAMMED+cell+death+1+receptors%22">PROGRAMMED cell death 1 receptors</searchLink><br /><searchLink fieldCode="DE" term="%22AUTOIMMUNE+diseases%22">AUTOIMMUNE diseases</searchLink><br /><searchLink fieldCode="DE" term="%22ADVERSE+health+care+events%22">ADVERSE health care events</searchLink><br /><searchLink fieldCode="DE" term="%22PHARMACODYNAMICS%22">PHARMACODYNAMICS</searchLink><br /><searchLink fieldCode="DE" term="%22DISEASE+risk+factors%22">DISEASE risk factors</searchLink>
– Name: Abstract
  Label: Abstract
  Group: Ab
  Data: Simple Summary: This review comprehensively summarizes the pathogenic mechanisms responsible for immune-related Adverse Events (irAEs) arising from self-tolerance loss due to Immune Checkpoint Inhibitors (ICIs) and discusses the main clinical manifestations due to irAEs categorized by organ types, their incidence, and risk factors. In addition, it focuses on the different distributions in frequencies of the diverse clinical manifestations due to irAEs between CTLA4 and PD1 pathway inhibitors and the intricate differential with primary autoimmune disorders, which share some pathophysiological and clinical aspects. The landscape of cancer treatment has undergone a significant transformation with the introduction of Immune Checkpoint Inhibitors (ICIs). Patients undergoing these treatments often report prolonged clinical and radiological responses, albeit with a potential risk of developing immune-related adverse events (irAEs). Here, we reviewed and discussed the mechanisms of action of ICIs and their pivotal role in regulating the immune system to enhance the anti-tumor immune response. We scrutinized the intricate pathogenic mechanisms responsible for irAEs, arising from the evasion of self-tolerance checkpoints due to drug-induced immune modulation. We also summarized the main clinical manifestations due to irAEs categorized by organ types, detailing their incidence and associated risk factors. The occurrence of irAEs is more frequent when ICIs are combined; with neurological, cardiovascular, hematological, and rheumatic irAEs more commonly linked to PD1/PD-L1 inhibitors and cutaneous and gastrointestinal irAEs more prevalent with CTLA4 inhibitors. Due to the often-nonspecific signs and symptoms, the diagnosis of irAEs (especially for those rare ones) can be challenging. The differential with primary autoimmune disorders becomes sometimes intricate, given the clinical and pathophysiological similarities. In conclusion, considering the escalating use of ICIs, this area of research necessitates additional clinical studies and practical insights, especially the development of biomarkers for predicting immune toxicities. In addition, there is a need for heightened education for both clinicians and patients to enhance understanding and awareness. [ABSTRACT FROM AUTHOR]
– Name: Abstract
  Label:
  Group: Ab
  Data: <i>Copyright of Cancers is the property of MDPI and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.)
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        Value: 10.3390/cancers16071440
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        Text: English
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      – SubjectFull: RISK assessment
        Type: general
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              Text: Apr2024
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