Data on the modulatory effects of a single bolus dexamethasone on the surface marker expression of various leucocyte subsets

Draxler, Dominik F.; Bain, Chris; Taylor, Rachael L.; Wallace, Sophia; Gouldthorpe, Oliver; Corcoran, Tomás; Myles, Paul S.; Bozaoglu, Kiymet; Medcalf, Robert L.

doi:10.1016/j.dib.2020.106117

Cited by 4 publications

(3 citation statements)

References 2 publications

(4 reference statements)

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“…GILZ is upregulated by DEX treatment in human DCs and induces a tolerant DC phenotype, increasing the expression of PD-L1. In vivo studies using healthy subjects demonstrate that DEX treatment increases PD-L1 expression in human DCs [ 129 ]. Accordingly, upregulation of GILZ via DEX increases the expression of PD-L1 in human DCs [ 130 ] and is required for in vitro PD-L1 expression [ 131 ].…”

Section: Gc and Pd-1/pd-l1 Pathways In Health And Cancermentioning

confidence: 99%

“…However, there is no current evidence for GR’s transcriptional regulation of PD-L1 in DCs. Conversely, in vitro studies, in contrast to in vivo observations [ 129 ], demonstrate that GCs do not alter PD-L1 expression in DC cells [ 134 , 135 ]. The activity of GCs on DC is, therefore, immunosuppressive, both directly and through GILZ-induced PD-L1 expression, thus favoring tumor immune escape.…”

Section: Gc and Pd-1/pd-l1 Pathways In Health And Cancermentioning

confidence: 99%

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Glucocorticoid and PD-1 Cross-Talk: Does the Immune System Become Confused?

Adorisio

Cannarile

Delfino

et al. 2021

Cells

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Programmed cell death protein 1 (PD-1) and its ligands, PD-L1/2, control T cell activation and tolerance. While PD-1 expression is induced upon T cell receptor (TCR) activation or cytokine signaling, PD-L1 is expressed on B cells, antigen presenting cells, and on non-immune tissues, including cancer cells. Importantly, PD-L1 binding inhibits T cell activation. Therefore, the modulation of PD-1/PD-L1 expression on immune cells, both circulating or in a tumor microenvironment and/or on the tumor cell surface, is one mechanism of cancer immune evasion. Therapies that target PD-1/PD-L1, blocking the T cell-cancer cell interaction, have been successful in patients with various types of cancer. Glucocorticoids (GCs) are often administered to manage the side effects of chemo- or immuno-therapy, exerting a wide range of immunosuppressive and anti-inflammatory effects. However, GCs may also have tumor-promoting effects, interfering with therapy. In this review, we examine GC signaling and how it intersects with PD-1/PD-L1 pathways, including a discussion on the potential for GC- and PD-1/PD-L1-targeted therapies to “confuse” the immune system, leading to a cancer cell advantage that counteracts anti-cancer immunotherapy. Therefore, combination therapies should be utilized with an awareness of the potential for opposing effects on the immune system.

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Section: Gc and Pd-1/pd-l1 Pathways In Health And Cancermentioning

confidence: 99%

Section: Gc and Pd-1/pd-l1 Pathways In Health And Cancermentioning

confidence: 99%

Glucocorticoid and PD-1 Cross-Talk: Does the Immune System Become Confused?

Adorisio

Cannarile

Delfino

et al. 2021

Cells

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“…In addition, Fk506 upregulates the action of glucocorticoids (GCs), 43,44 which were demonstrated to be involved in PD‐L1 regulation 45 . GCs can enhance the expression of PD‐L1 in DCs through the GC‐induced leucine zipper 46 and prevent antigen‐specific T lymphocyte response 47 . Furthermore, the GC receptor can regulate PD‐L1 and MHC‐I in pancreatic cancer cells to promote immune evasion and immunotherapy resistance 48 .…”

Section: Discussionmentioning

confidence: 99%

Novel immunosuppressive effect of FK506 by upregulation of PD‐L1 via FKBP51 in heart transplantation

Luo

Du²,

Chen³

et al. 2022

Scand J Immunol

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The calcineurin inhibitor–FK506–is a first‐line immunosuppressant that regulates T cell secretion of IL‐2 and other cytokines. However, the mechanism of its protective effect on target cells and its role on tumour recurrence and interaction with anti‐tumour immune checkpoint inhibitors, such as PD‐L1 blocking, are still unclear. Here, in a murine heart transplantation model, we observed the upregulation of programmed death‐ligand 1 (PD‐L1) expression by FK506 in both dendritic cells (DCs) and allografts. Blocking PD‐L1 during FK506 treatment increased IFN‐γ and TNF‐α expression, enhanced CD4+ and CD8+ T cell proliferation, and suppressed Treg differentiation. Moreover, PD‐L1 decreased T cell infiltration and induced T cell apoptosis in both the spleen and graft. PD‐L1 was not only required in FK506‐mediated immunosuppression but also upregulated by FK506. Treatment with SAFit2, a FKBP51 selective inhibitor, reduced the expression of PD‐L1 on DCs and the grafts and interfered with the immunosuppressive effect of FK506, suggesting that the mechanism depends on FK506‐binding protein (FKBP) 51 expression. Overall, our results add new insights into the role of FK506, not only on T cell cytokine secretion but also on co‐inhibitory molecular regulation and target cell immune privilege.

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