IMMUNOTHERAPY WITH CHECKPOINT INHIBITORS (ICPI) AND IMMUNE RELATED ADVERSE EVENTS (IRAE'S)
INTRODUCTION: In recent years, considerable progress has been achieved in understanding the interaction between malignant cells and immune cells. The immune system continually seeks out and destroys mutated cells, but in some cases, mutations may occur and give some malignant cells the advantage to neutralize and evade the immune system. One of the regulatory mechanisms that allows these cells to abrogate immune responses is based on Immune Checkpoints. These checkpoints include the Cytotoxic-T lymphocyte antigen-4 (CTLA-4), Programmed cell death protein-1 (PD-1) and its ligand Programmed death-ligand-1 (PD-L1). Tasuku Honjo and James Allison, 2018 Nobel Prize laureates, investigated various components of these mechanisms. They found that in some cases malignant cells may overexpress binding sites that interact with CTLA-4 or PD-1, like the PD-L1 molecule, thus managing to maneuver the immune system. They paved the way for a new class of cancer drugs by showing different strategies to disrupt these checkpoints. This understanding has prompted a paradigm shift in oncology and a breakthrough in the development of new generation immunotherapy drugs: Immune Checkpoint Inhibitors (ICPi). By unbalancing the immune system, these treatments also generated dysimmune toxicities, called Immune Related Adverse Events (irAEs). The study of irAEs is in its infancy; there are very few prospective studies. Where possible, the estimates of irAE incidence were drawn from meta-analyses of randomized controlled trials. In this article, we discuss the connection between immune system, autoimmunity and cancer; immune checkpoint inhibitors and associated autoimmune toxicities; the impact of autoimmune manifestations on cancer outcome and management of irAEs.
| Medienart: |
Artikel |
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| Erscheinungsjahr: |
2020 |
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| Erschienen: |
2020 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:159 |
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| Enthalten in: |
Harefuah - 159(2020), 7 vom: 21. Juli, Seite 508-515 |
| Sprache: |
Hebräisch |
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| Beteiligte Personen: |
Ben Zvi, Carina [VerfasserIn] |
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| Themen: |
Antineoplastic Agents, Immunological |
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| Anmerkungen: |
Date Completed 31.07.2020 Date Revised 31.07.2020 published: Print Citation Status MEDLINE |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM312965621 |
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| 520 | |a INTRODUCTION: In recent years, considerable progress has been achieved in understanding the interaction between malignant cells and immune cells. The immune system continually seeks out and destroys mutated cells, but in some cases, mutations may occur and give some malignant cells the advantage to neutralize and evade the immune system. One of the regulatory mechanisms that allows these cells to abrogate immune responses is based on Immune Checkpoints. These checkpoints include the Cytotoxic-T lymphocyte antigen-4 (CTLA-4), Programmed cell death protein-1 (PD-1) and its ligand Programmed death-ligand-1 (PD-L1). Tasuku Honjo and James Allison, 2018 Nobel Prize laureates, investigated various components of these mechanisms. They found that in some cases malignant cells may overexpress binding sites that interact with CTLA-4 or PD-1, like the PD-L1 molecule, thus managing to maneuver the immune system. They paved the way for a new class of cancer drugs by showing different strategies to disrupt these checkpoints. This understanding has prompted a paradigm shift in oncology and a breakthrough in the development of new generation immunotherapy drugs: Immune Checkpoint Inhibitors (ICPi). By unbalancing the immune system, these treatments also generated dysimmune toxicities, called Immune Related Adverse Events (irAEs). The study of irAEs is in its infancy; there are very few prospective studies. Where possible, the estimates of irAE incidence were drawn from meta-analyses of randomized controlled trials. In this article, we discuss the connection between immune system, autoimmunity and cancer; immune checkpoint inhibitors and associated autoimmune toxicities; the impact of autoimmune manifestations on cancer outcome and management of irAEs | ||
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