Back to Search
Start Over
Mechanistic insights into immune checkpoint inhibitor-related hypophysitis: a form of paraneoplastic syndrome
- Source :
- Cancer Immunology, Immunotherapy
- Publication Year :
- 2021
- Publisher :
- Springer, 2021.
-
Abstract
- Background Immune checkpoint inhibitors (ICIs) as a cancer immunotherapy have emerged as a treatment for multiple advanced cancer types. Because of enhanced immune responses, immune-related adverse events (irAEs), including endocrinopathies such as hypophysitis, have been associated with the use of ICIs. Most underlying mechanisms of ICI-related hypophysitis remain unclear, especially for programmed cell death-1 (PD-1)/PD-1 ligand 1 (PD-L1) inhibitors. We hypothesized that ICI-related hypophysitis is associated with paraneoplastic syndrome caused by ectopic expression of pituitary-specific antigens. Methods Twenty consecutive patients with ICI-related hypophysitis between 2017 and 2019 at Kobe University Hospital were retrospectively analyzed. Circulating anti-pituitary antibodies were detected using immunofluorescence staining and immunoblotting. Ectopic expression of pituitary autoantigens in tumor specimens was also examined. Results Eighteen patients were treated with PD-1/PD-L1 inhibitors, and two were treated with a combination of cytotoxic T-lymphocyte antigen-4 (CTLA-4) and PD-1 inhibitors. All patients showed adrenocorticotropic hormone (ACTH) deficiency and additionally, three showed thyroid-stimulating hormone (TSH) deficiency, and one showed gonadotropin-releasing hormone (GnRH) deficiency. Among these patients, three exhibited anti-pituitary antibodies, two with anti-corticotroph antibody and one with anti-somatotroph antibody. Interestingly, the anti-corticotroph antibody recognized proopiomelanocortin (POMC) and those two patients exhibited ectopic ACTH expression in the tumor, while the patients without anti-corticotroph antibody did not. Conclusions We demonstrated 10% of PD-1/PD-L1 inhibitors-related hypophysitis were associated with the autoimmunity against corticotrophs and maybe caused as a form of paraneoplastic syndrome, in which ectopic expression of ACTH in the tumor was observed. It is also suggested that the pathophysiology is heterogenous in ICI-related hypophysitis.
- Subjects :
- Male
Cancer Research
Pro-Opiomelanocortin
Paraneoplastic Syndromes
Programmed Cell Death 1 Receptor
Autoimmunity
Hypopituitarism
Immune checkpoint inhibitor
medicine.disease_cause
B7-H1 Antigen
Mice
0302 clinical medicine
Neoplasms
Immunology and Allergy
CTLA-4 Antigen
Corticotrophs
Immune Checkpoint Inhibitors
Aged, 80 and over
biology
Middle Aged
Oncology
030220 oncology & carcinogenesis
Paraneoplastic syndrome
Female
Original Article
Immunotherapy
Antibody
hormones, hormone substitutes, and hormone antagonists
Adult
endocrine system
Hypophysitis
Immunology
030209 endocrinology & metabolism
Adrenocorticotropic hormone
03 medical and health sciences
Antigen
medicine
Animals
Humans
Aged
Retrospective Studies
business.industry
medicine.disease
biology.protein
Ectopic expression
Corticotropic cell
business
Adrenal Insufficiency
Subjects
Details
- Language :
- English
- ISSN :
- 03407004
- Volume :
- 70
- Issue :
- 12
- Database :
- OpenAIRE
- Journal :
- Cancer Immunology, Immunotherapy
- Accession number :
- edsair.doi.dedup.....3acc181a81511e7fe6b828ea748faa32