V H Koelzer1,2, K Glatz3, L Bubendorf3, A Weber4, A Gaspert4, G Cathomas1, A Lugli5, A Zippelius6, W Kempf7, K D Mertz8. 1. Institut für Pathologie, Kantonsspital Baselland, Mühlemattstraße 11, 4410, Liestal, Schweiz. 2. Translational Research Unit (TRU), Institut für Pathologie, Universität Bern, Bern, Schweiz. 3. Institut für Pathologie, Universitätsspital Basel, Basel, Schweiz. 4. Institut für Pathologie und Molekularpathologie, Universität Zürich und Universitätsspital Zürich, Zürich, Schweiz. 5. Klinische Pathologie, Institut für Pathologie, Universität Bern, Bern, Schweiz. 6. Klinik für Onkologie, Universitätsspital Basel, Basel, Schweiz. 7. Kempf und Pfaltz Histologische Diagnostik, Research Unit, Zürich, Schweiz. 8. Institut für Pathologie, Kantonsspital Baselland, Mühlemattstraße 11, 4410, Liestal, Schweiz. kirsten.mertz@ksbl.ch.
Abstract
BACKGROUND: Immunotherapy has gained importance with the development of new effective cancer treatments. Immune checkpoint inhibitors (ICI) are monoclonal antibodies that promote T‑cell mediated tumor immune rejection. Checkpoint blockade also carries the risk of inducing autoimmune reactions ("immune related adverse events", irAEs). The diagnosis and classification of irAEs constitute a new and important field in pathology. AIM: Practice-oriented review of the diagnosis and classification of irAEs. MATERIALS AND METHODS: Structured, selective literature review based on PubMed und UpToDate ® online. RESULTS: The most common irAEs affect the skin, the gastrointestinal tract, the liver, and the respiratory system. The correct diagnosis and classification of irAEs by an interdisciplinary care team is essential for appropriate therapy and the prevention of long-term sequelae. Other important irAEs affect the endocrine organs, the heart, the joints, the kidneys and the nervous system. Because of their rarity and/or limited options for bioptic diagnosis, only limited data on the morphology and pathophysiology of these irAEs are currently available. Autopsies carried out after ICI therapy constitute an important element of quality control and allow better documentation of the incidence and pathogenesis of irAEs. DISCUSSION: Pathology plays a central role in the diagnosis and treatment of irAEs. Future studies may contribute to a better mechanistic understanding of irAEs for individualized knowledge-based risk assessment.
BACKGROUND: Immunotherapy has gained importance with the development of new effective cancer treatments. Immune checkpoint inhibitors (ICI) are monoclonal antibodies that promote T‑cell mediated tumor immune rejection. Checkpoint blockade also carries the risk of inducing autoimmune reactions ("immune related adverse events", irAEs). The diagnosis and classification of irAEs constitute a new and important field in pathology. AIM: Practice-oriented review of the diagnosis and classification of irAEs. MATERIALS AND METHODS: Structured, selective literature review based on PubMed und UpToDate ® online. RESULTS: The most common irAEs affect the skin, the gastrointestinal tract, the liver, and the respiratory system. The correct diagnosis and classification of irAEs by an interdisciplinary care team is essential for appropriate therapy and the prevention of long-term sequelae. Other important irAEs affect the endocrine organs, the heart, the joints, the kidneys and the nervous system. Because of their rarity and/or limited options for bioptic diagnosis, only limited data on the morphology and pathophysiology of these irAEs are currently available. Autopsies carried out after ICI therapy constitute an important element of quality control and allow better documentation of the incidence and pathogenesis of irAEs. DISCUSSION: Pathology plays a central role in the diagnosis and treatment of irAEs. Future studies may contribute to a better mechanistic understanding of irAEs for individualized knowledge-based risk assessment.
Entities:
Keywords:
Adverse drug event; Autoimmunity; Immunotherapy; Personalized medicine
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