المؤلفون: Galligan, Anna, Iravani, Amir, Lasocki, Arian, Wallace, Roslyn, Weppler, Alison M., Sachithanandan, Nirupa, Chiang, Cherie, Colman, Peter G., Wentworth, John, Spain, Lavinia, Au-Yeung, George, Lee, Belinda, Kay, Thomas W. H., Hicks, Rodney J., Sandhu, Shahneen, Krishnamurthy, Balasubramanian

المصدر: Frontiers in Endocrinology; 2023, p1-10, 10p

مصطلحات موضوعية: POSITRON emission tomography computed tomography, IMMUNE checkpoint inhibitors, MAGNETIC resonance imaging, CANCER treatment, GLANDS, IMMUNE response, PITUITARY gland

مستخلص: Introduction: Hypophysitis is reported in 8.5%-14% of patients receiving combination immune checkpoint inhibition (cICI) but can be a diagnostic challenge. This study aimed to assess the role of routine diagnostic imaging performed during therapeutic monitoring of combination anti-CTLA-4/anti-PD-1 treatment in the identification of hypophysitis and the relationship of imaging findings to clinical diagnostic criteria. Methods: This retrospective cohort study identified patients treated with cICI between January 2016 and January 2019 at a quaternary melanoma service. Medical records were reviewed to identify patients with a documented diagnosis of hypophysitis based on clinical criteria. Available structural brain imaging with magnetic resonance imaging (MRI) or computed tomography (CT) of the brain and 2-deoxy-2-[18F]fluoro-D-glucose positron emission tomography with computed tomography (FDG-PET/CT) were assessed retrospectively. The main radiological outcome measures were a relative change in pituitary size or FDG uptake temporally attributed to cICI. Results: There were 162 patients (median age 60 years, 30% female) included. A total of 100 and 134 had serial CT/MRI of the brain and FDG-PET/CT, respectively. There were 31 patients who had a documented diagnosis of hypophysitis and an additional 20 who had isolated pituitary imaging findings. The pituitary gland enlargement was mild, and the largest absolute gland size was 13 mm, with a relative increase of 7 mm from baseline. There were no cases of optic chiasm compression. Pituitary enlargement and increased FDG uptake were universally transient. High-dose glucocorticoid treatment for concurrent irAEs prevented assessment of the pituitary-adrenal axis in 90% of patients with isolated imaging findings. Conclusion: Careful review of changes in pituitary characteristics on imaging performed for assessment of therapeutic response to iICI may lead to increased identification and more prompt management of cICI-induced hypophysitis. [ABSTRACT FROM AUTHOR]

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المؤلفون: Zhang, Yuxia, Maksimovic, Jovana, Huang, Bing, De Souza, David Peter, Naselli, Gaetano, Chen, Huan, Zhang, Li, Weng, Kai, Liang, Hanquan, Xu, Yanhui, Wentworth, John M., Huntington, Nicholas D., Oshlack, Alicia, Gong, Sitang, Kallies, Axel, Vuillermin, Peter, Yang, Min, Harrison, Leonard C.

المصدر: Frontiers in Immunology; 4/25/2018, p1-N.PAG, 13p

مصطلحات موضوعية: FATTY acids, METABOLISM, PHENOTYPES

مستخلص: How T cells differentiate in the neonate may critically determine the ability of the infant to cope with infections, respond to vaccines and avert allergies. Previously, we found that naïve cord blood CD4⁺ T cells differentiated toward an IL-4-expressing phenotype when activated in the presence of TGF-β and monocyte-derived inflammatory cytokines, the latter are more highly secreted by infants who developed food allergy. Here, we show that in the absence of IL-2 or IL-12, naïve cord blood CD8⁺ T cells have a natural propensity to differentiate into IL-4-producing non-classic TC2 cells when they are activated alone, or in the presence of TGF-β and/or inflammatory cytokines. Mechanistically, non-classic TC2 development is associated with decreased expression of IL-2 receptor alpha (CD25) and glycolysis, and increased fatty acid metabolism and caspase-dependent cell death. Consequently, the short chain fatty acid, sodium propionate (NaPo), enhanced IL-4 expression, but exogenous IL-2 or pan-caspase inhibition prevented IL-4 expression. In children with endoscopically and histologically confirmed non-inflammatory bowel disease and non-infectious pediatric idiopathic colitis, the presence of TGF-β, NaPo, and IL-1β or TNF-α promoted TC2 differentiation in vitro. In vivo, colonic mucosa of children with colitis had significantly increased expression of IL-4 in CD8⁺ T cells compared with controls. In addition, activated caspase-3 and IL-4 were co-expressed in CD8⁺ T cells in the colonic mucosa of children with colitis. Thus, in the context of colonic inflammation and limited IL-2 signaling, CD8⁺ T cells differentiate into non-classic TC2 that may contribute to the pathology of inflammatory/allergic diseases in children. [ABSTRACT FROM AUTHOR]

: Copyright of Frontiers in Immunology is the property of Frontiers Media S.A. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)