期刊
JOURNAL OF IMMUNOTHERAPY
卷 28, 期 6, 页码 517-524出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/01.cji.0000177999.95831.7b
关键词
immunotherapy; glucocorticoid; T cell
资金
- Intramural NIH HHS [Z01 BC010763-01, Z99 CA999999] Funding Source: Medline
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 truce 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 anti-tumor 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 pinel-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, gucocorticoids had a profound inhibitory effect oil 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.
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