Glucocorticoids upregulate FOXP3 expression and regulatory T cells in asthma

Karagiannidis, Christian; Akdiş, Mübeccel; Holopainen, Päivi; Woolley, N.; Hense, G.; Rückert, Beate; Mantel, Pierre‐Yves; Menz, G; Blaser, Kurt; Schmidt‐Weber, Carsten B.

doi:10.1016/j.jaci.2004.07.014

Cited by 444 publications

(328 citation statements)

References 44 publications

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“…The sensitivity of Treg cells to dexamethasone is controversial with multiple studies showing conflicting results. 26,32–36 Given this study’s findings, dexamethasone treatment could potentially have a positive influence on shaping antitumor immunity by reducing circulating Treg cell numbers and their subsequent tumor infiltration. 37 However, this potential positive influence must be counterbalanced with dexamethasone’s negative effects on conventional CD4+ and CD8+ T cells.…”

Section: Discussionmentioning

confidence: 85%

Contrasting impact of corticosteroids on anti-PD-1 immunotherapy efficacy for tumor histologies located within or outside the central nervous system

et al. 2018

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Immune checkpoint blockade targeting programmed cell death protein 1 (PD-1) is emerging as an important treatment strategy in a growing list of cancers, yet its clinical benefits are limited to a subset of patients. Further investigation of tumor-intrinsic predictors of response and how extrinsic factors, such as iatrogenic immunosuppression caused by conventional therapies, impact the efficacy of anti-PD-1 therapy are paramount. Given the widespread use of corticosteroids in cancer management and their immunosuppressive nature, this study sought to determine how corticosteroids influence anti-PD-1 responses and whether their effects were dependent on tumor location within the periphery versus central nervous system (CNS), which may have a more limiting immune environment. In well-established anti-PD-1-responsive murine tumor models, corticosteroid therapy resulted in systemic immune effects, including severe and persistent reductions in peripheral CD4+ and CD8 + T cells. Corticosteroid treatment was found to diminish the efficacy of anti-PD-1 therapy in mice bearing peripheral tumors with responses correlating with peripheral CD8/Treg ratio changes. In contrast, in mice bearing intracranial tumors, corticosteroids did not abrogate the benefits conferred by anti-PD-1 therapy. Despite systemic immune changes, anti-PD-1-mediated antitumor immune responses remained intact during corticosteroid treatment in mice bearing intracranial tumors. These findings suggest that anti-PD-1 responses may be differentially impacted by concomitant corticosteroid use depending on tumor location within or outside the CNS. As an immune-specialized site, the CNS may potentially play a protective role against the immunosuppressive effects of corticosteroids, thus sustaining antitumor immune responses mediated by PD-1 blockade.

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Section: Discussionmentioning

confidence: 85%

Contrasting impact of corticosteroids on anti-PD-1 immunotherapy efficacy for tumor histologies located within or outside the central nervous system

et al. 2018

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“…Induction of IL-10 expression has been suggested to contribute to the anti-inflammatory properties of GCs in rheumatoid arthritis (Verhoef et al, 1999), asthma (Karagiannidis et al, 2004;Stelmach et al, 2002), multiple sclerosis (Gayo et al, 1998) and cardiac bypass surgery (Tabardel et al, 1996). In these complex clinical settings the cellular source of IL-10 is often unclear.…”

Section: Il-10mentioning

confidence: 99%

Anti-inflammatory functions of glucocorticoid-induced genes

Clark

2007

Molecular and Cellular Endocrinology

238

193

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“…To date, Tregs are best characterized by FOXP3-expression, whose transcription is fundamental for both differentiation and function 8 , complemented by additional markers such as CD25, GITR, LAG3 or low CD127 expression [9][10][11] [12][13][14] . Indeed, successful treatment of allergy by allergen-specific immunotherapy may depend on induction of Tregs 6,15 .…”

Section: Introductionmentioning

confidence: 99%