Dexamethasone enhances programmed cell death 1 (PD-1) expression during T cell activation: an insight into the optimum application of glucocorticoids in anti-cancer therapy

• Published in: BMC immunology Vol. 16; no. 1; p. 39
• Main Authors: Xing, Kailin, Gu, Bingxin, Zhang, Ping, Wu, Xianghua
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 26.06.2015; BioMed Central
• Subjects: Animals; Antineoplastic Agents - pharmacology; Apoptosis - drug effects; Dexamethasone - pharmacology; Female; Glucocorticoids - pharmacology; Humans; Hydrocortisone - pharmacology; Kinetics; Lymphocyte Activation - drug effects; Mice, Inbred BALB C; Mifepristone - pharmacology; Programmed Cell Death 1 Receptor - genetics; Programmed Cell Death 1 Receptor - metabolism; RNA, Messenger - genetics; RNA, Messenger - metabolism; T-Lymphocytes - drug effects; T-Lymphocytes - immunology; Up-Regulation - drug effects
• ISSN: 1471-2172; 1471-2172
• DOI: 10.1186/s12865-015-0103-2

Programmed cell death 1 (PD-1) is a key cell-surface receptor of CD28 superfamily that triggers inhibitory pathways to attenuate T-cell responses and promote T-cell tolerance. As a crucial role in tumor immunity, PD-1 has been a focus of studies in anti-cancer therapy. It has been approved that tumors could exploit PD-1-dependent immune suppression for immune evasion. Considering the wide use of glucocorticoids (GCs) in anti-cancer therapy and their immunosuppressive effects, we explored whether GCs could influence the expression of PD-1. In our study, we used dexamethasone (DEX) as a model glucocorticoid and demonstrated that DEX could enhance PD-1 expression in a dose-dependent manner. The effects were completely inhibited by the glucocorticoid receptor (GR) antagonist mifepristone (RU486), indicating that the effect of DEX on PD-1 is mediated through GR. We further found the sensitivity to DEX-induced upregulation of PD-1 expression had a significant difference between different T cell subsets, with memory T cells more susceptible to this effect. We also showed that DEX could suppress T cell functions via inhibition of cytokines production such as IL-2, IFN-γ, TNF-α and induction of apoptosis of T cells. Our findings suggest a novel way by which DEX suppress the function of activated T lymphocytes by enhancing expression of PD-1 and provide an insight into the optimum clinical application of GCs.