Format

Send to

Choose Destination
J Immunother. 2005 Nov-Dec;28(6):517-24.

Glucocorticoids do not inhibit antitumor activity of activated CD8+ T cells.

Author information

1
National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, Maryland 20892-1502, USA.

Abstract

Glucocorticoids are potent immunosuppressive drugs that are generally withheld from cancer patients receiving immunotherapy. We sought to test the hypothesis that glucocorticoids might interfere with the function of cells after adoptive transfer. We gave dexamethasone, a potent synthetic glucocorticoid, to B16 melanoma-bearing mice receiving the adoptive cell transfer (ACT) of pmel-1 T-cell receptor transgenic CD8+ cells. Dexamethasone caused a profound lymphodepletion but, surprisingly, did not alter the antitumor efficacy of ACT-based regimens whether given before, during, or after ACT. Although dexamethasone radically decreased the number of native CD8+ splenocytes in recipient mice, it did not affect the numbers of CD8+ pmel-1 cells derived from ACT in these mice. In vitro proliferation assays revealed acute inhibition of naive pmel-1 CD8+ cells by dexamethasone without significant effect on activated cells. In vitro interferon (IFN)-gamma release from activated pmel-1 CD8+ cells showed partial inhibition by dexamethasone, but this effect was relatively minor when compared with the near-complete inhibition of naive cells. Thus, glucocorticoids had a profound inhibitory effect on naive CD8+ T cells but had little impact on the proliferation and function of activated CD8+ pmel-1 T cells. Finally, because glucocorticoids had no effect on tumor regression in this model, it may be possible to use glucocorticoids in some patients receiving ACT-based immunotherapy regimens.

[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Wolters Kluwer Icon for PubMed Central
Loading ...
Support Center