Treatment with tumor necrosis factor-α and granulocyte-macrophage colony-stimulating factor increases epidermal Langerhans' cell numbers in cancer patients

被引:21
作者
Janik, JE
Miller, LL
Kopp, WC
Taub, DD
Dawson, H
Stevens, D
Kostboth, P
Curti, BD
Conlon, KC
Dunn, BK
Donegan, SE
Ullrich, R
Alvord, WG
Gause, BL
Longo, DL
机构
[1] NCI, Frederick Canc Res & Dev Ctr, Biol Response Modifiers Programme, Frederick, MD 21701 USA
[2] NCI, Frederick Canc Res & Dev Ctr, SAIC Frederick, Clin Serv Program, Frederick, MD 21702 USA
[3] NCI, Frederick Canc Res & Dev Ctr, SAIC Frederick, Data Management Serv Inc, Frederick, MD 21702 USA
[4] Reeders Mem Home, Boonsboro, MD USA
[5] Frederick Mem Hosp, Frederick, MD 21701 USA
[6] USA, Med Res Inst Infect Dis, Dept Immunol & Mol Biol, Ft Detrick, MD 21702 USA
关键词
D O I
10.1006/clim.1999.4778
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Dendritic cells (DCs) initiate primary and stimulate secondary T-cell responses. We conducted a phase I trial of tumor necrosis factor (TNF-alpha) and granulocyte-macrophage colony-stimulating factor (GM-CSF) in patients with cancer to increase DCs in peripheral blood or skin based on in vitro data that showed that CD34(+) hematopoietic precursors require these cytokines to mature into functional antigen-presenting DCs. Eleven patients mere treated for 7 days with GM-CSF, 125 mu g/m(2) twice daily as subcutaneous injections, and TNF-alpha as a continuous infusion at dose levels of 25, 50, or 100 mu g/m(2)/day. The maximum tolerated dose of TNF-alpha was 50 mu g/m(2)/day with this dose of GM-CSF; dose-limiting toxicities occurred in both patients treated with 100 mu g/m(2)/day. One became thrombocytopenic and the other had transient confusion. Epidermal Langerhans' cells were quantitated by S100 staining of skin biopsies and DC precursors in peripheral blood by colony-forming unit dendritic (CFU-dendritic) assays. S100-positive cells in the epidermis doubled after treatment (2.55 S100(+) cells/high-powerheld before treatment to 6.05 after treatment, p = 0.029). CFU-dendritic in peripheral blood increased after treatment in 3 colorectal cancer patients but not in 3 patients with melanoma. CD11c(+) or CD123(+), HLA-DRbright, lineage-negative dendritic cell precursors were not increased in peripheral blood mononuclear cells. This trial demonstrates that treatment with TNF-alpha and GM-CSF can increase the number of DCs in the skin and the number of dendritic cell precursors in the blood of some patients with cancer. This approach may increase the efficacy of vaccination to tumor antigens in cancer patients.
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收藏
页码:209 / 221
页数:13
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