[Endocrine Organ Dysfunction with Immune-Checkpoint Inhibitors].

Abstract

Cytotoxic T-lymphocyte associated antigen 4(CTLA-4), programmed death 1(PD-1), and programmed death-ligand 1 (PD-L1)are referred to as immune-checkpoints. CTLA-4 is located on the surface of activated T-cells, therefore inhibiting binding of CD28 to B7 molecule on antigen presenting cells. The CTLA-4 pathway predominantly acts in lymph nodes. PD-1 is majorly expressed on T-cells. The PD-1 pathway is involved with tumor microenvironment. Immune-checkpoint inhibitors (ICIs)are monoclonal antibodies to these molecules and are promising novel agents for malignant tumor treatment. ICIs promote T-cell-mediated cytotoxicity directed at cancer cell antigens. Approximately 20-30% of patients with advanced cancer were found to be responders of ICIs. However, various adverse events have been reported as immune-related adverse events(irAEs). IrAEs include dermatological, gastrointestinal, hepatic, neurological, and endocrine disorders. In the endocrine system, irAEs in the pituitary glands, thyroid glands, pancreas, and adrenal glands have been reported. Since rapidly progressive fatal endocrine systems failure may provoke during ICI therapy, precise diagnosis and prompt treatment as well as close follow-up is critical. We propose routine monitoring of endocrine functions and related symptoms(ie. worsened fatigue, hyperglycemia, hypoglycemia, hypotension, and hyponatremia), as well as other laboratory tests during ICI therapy. We herein discuss possible mechanisms of endocrine irAEs with ICIs, and highlight diagnostic approaches, treatments, and future prospects of endocrine irAEs during ICI therapy.

• Authors: Hidefumi Inaba, Hiroyuki Ariyasu, Chiaki Kurimoto, Hiroshi Iwakura, Takashi Akamizu
• Journal: Gan to kagaku ryoho. Cancer & chemotherapy (Gan To Kagaku Ryoho) Vol. 45 Issue 7 Pg. 1031-1035 (Jul 2018) ISSN: 0385-0684 [Print] Japan
• PMID: 30042266 (Publication Type: Journal Article)

Chemical References

• Antineoplastic Agents

Topics

• Antineoplastic Agents (adverse effects, therapeutic use)
• Endocrine System Diseases (chemically induced, metabolism, physiopathology)
• Humans
• Molecular Targeted Therapy (adverse effects)
• Neoplasms (drug therapy, immunology)