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

BMC Immunol. 2015 Jun 26;16:39. doi: 10.1186/s12865-015-0103-2.


Background: 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.

Results: 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.

Conclusion: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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


  • Antineoplastic Agents
  • Glucocorticoids
  • PDCD1 protein, human
  • Pdcd1 protein, mouse
  • Programmed Cell Death 1 Receptor
  • RNA, Messenger
  • Mifepristone
  • Dexamethasone
  • Hydrocortisone