Mechanistic insights into immune checkpoint inhibitor-related hypophysitis: a form of paraneoplastic syndrome

• DOI: 10.1007/s00262-021-02955-y
• Publication Date: 2021-05-11T18:02:37Z
• Authors: Keitaro Kanie; Genzo Iguchi; Hironori Bando; Shin Urai; Hiroki Shichi; Yasunori Fujita; Ryusaku Matsumoto; Kentaro Suda; Masaaki Yamamoto; Hidenori Fukuoka; Wataru Ogawa; Yutaka Takahashi
• Keywords: Corticotropic cell; Hypophysitis; Proopiomelanocortin; Blocking antibody

Immune checkpoint inhibitors (ICIs) as a cancer immunotherapy have emerged treatment for multiple advanced types. Because of enhanced immune responses, immune-related adverse events (irAEs), including endocrinopathies such hypophysitis, been associated with the use ICIs. Most underlying mechanisms ICI-related hypophysitis remain unclear, especially programmed cell death-1 (PD-1)/PD-1 ligand 1 (PD-L1) inhibitors. We hypothesized that is paraneoplastic syndrome caused by ectopic expression pituitary-specific antigens.Twenty consecutive patients between 2017 and 2019 at Kobe University Hospital were retrospectively analyzed. Circulating anti-pituitary antibodies detected using immunofluorescence staining immunoblotting. Ectopic pituitary autoantigens in tumor specimens was also examined.Eighteen treated PD-1/PD-L1 inhibitors, two combination cytotoxic T-lymphocyte antigen-4 (CTLA-4) PD-1 All showed adrenocorticotropic hormone (ACTH) deficiency additionally, three thyroid-stimulating (TSH) deficiency, one gonadotropin-releasing (GnRH) deficiency. Among these patients, exhibited antibodies, anti-corticotroph antibody anti-somatotroph antibody. Interestingly, recognized proopiomelanocortin (POMC) those ACTH tumor, while without did not.We demonstrated 10% inhibitors-related autoimmunity against corticotrophs maybe form syndrome, which observed. It suggested pathophysiology heterogenous hypophysitis.