Abstract | CONTEXT: In recent years, progress has been made in cancer immunotherapy by the development of drugs acting as modulators of immune checkpoint proteins, such as the cytotoxic T-lymphocyte antigen-4 (CTLA4) and programmed death-1 (PD-1), two co-inhibitory receptors that are expressed on T cells upon activation. These molecules play crucial roles in maintaining immune homeostasis by down-regulating T-cell signaling, thereby preventing unbridled T-cell proliferation while maintaining tolerance to self-antigens, such as tumor-associated antigens. CTLA4 blockade through systemic administration of the CTLA4-blocking antibody ipilimumab was shown to confer significant survival benefit and prolonged stable disease in patients affected by advanced cutaneous melanoma. Other immune checkpoint inhibitors are under clinical evaluation. However, immune checkpoint blockade can lead to the breaking of immune self-tolerance, thereby inducing a novel syndrome of autoimmune/autoinflammatory side effects, designated as "immune-related adverse events," mainly including rash, colitis, hepatitis, and endocrinopathies. DATA ACQUISITION: EVIDENCE SYNTHESIS: CONCLUSIONS: Although reports of endocrine side effects caused by cancer immune therapy are abundant, their exact prevalence and mechanism are unclear. Well-designed correlative studies oriented to finding and validating predictive factors of autoimmune toxicity are urgently needed.
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Authors | Salvatore Maria Corsello, Agnese Barnabei, Paolo Marchetti, Liana De Vecchis, Roberto Salvatori, Francesco Torino |
Journal | The Journal of clinical endocrinology and metabolism
(J Clin Endocrinol Metab)
Vol. 98
Issue 4
Pg. 1361-75
(Apr 2013)
ISSN: 1945-7197 [Electronic] United States |
PMID | 23471977
(Publication Type: Evaluation Study, Journal Article, Review)
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Chemical References |
- Antibodies, Monoclonal
- Antineoplastic Agents
- CTLA-4 Antigen
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Topics |
- Antibodies, Monoclonal
(adverse effects, therapeutic use)
- Antineoplastic Agents
(adverse effects, therapeutic use)
- CTLA-4 Antigen
(antagonists & inhibitors, immunology)
- Cell Cycle Checkpoints
(immunology)
- Drug-Related Side Effects and Adverse Reactions
(chemically induced, epidemiology)
- Endocrine System
(drug effects)
- Endocrine System Diseases
(chemically induced, epidemiology)
- Humans
- Immunotherapy
(adverse effects)
- Neoplasms
(therapy)
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