PMID- 10600331
OWN - NLM
STAT- MEDLINE
DCOM- 20000104
LR  - 20041117
IS  - 1521-6616 (Print)
IS  - 1521-6616 (Linking)
VI  - 93
IP  - 3
DP  - 1999 Dec
TI  - Treatment with tumor necrosis factor-alpha and granulocyte-macrophage 
      colony-stimulating factor increases epidermal Langerhans' cell numbers in cancer 
      patients.
PG  - 209-21
AB  - 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 were treated for 7 days with 
      GM-CSF, 125 microg/m(2) twice daily as subcutaneous injections, and TNF-alpha as 
      a continuous infusion at dose levels of 25, 50, or 100 microg/m(2)/day. The 
      maximum tolerated dose of TNF-alpha was 50 microg/m(2)/day with this dose of 
      GM-CSF; dose-limiting toxicities occurred in both patients treated with 100 
      microg/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-power field 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-DR(bright), 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.
FAU - Janik, J E
AU  - Janik JE
AD  - Biological Response Modifiers Program, NCI-FCRDC, 501 W. Seventh Street, Suite 3, 
      Frederick, Maryland 21701-4507, USA.
FAU - Miller, L L
AU  - Miller LL
FAU - Kopp, W C
AU  - Kopp WC
FAU - Taub, D D
AU  - Taub DD
FAU - Dawson, H
AU  - Dawson H
FAU - Stevens, D
AU  - Stevens D
FAU - Kostboth, P
AU  - Kostboth P
FAU - Curti, B D
AU  - Curti BD
FAU - Conlon, K C
AU  - Conlon KC
FAU - Dunn, B K
AU  - Dunn BK
FAU - Donegan, S E
AU  - Donegan SE
FAU - Ullrich, R
AU  - Ullrich R
FAU - Alvord, W G
AU  - Alvord WG
FAU - Gause, B L
AU  - Gause BL
FAU - Longo, D L
AU  - Longo DL
LA  - eng
PT  - Clinical Trial
PT  - Clinical Trial, Phase I
PT  - Journal Article
PL  - United States
TA  - Clin Immunol
JT  - Clinical immunology (Orlando, Fla.)
JID - 100883537
RN  - 0 (Carcinoembryonic Antigen)
RN  - 0 (Recombinant Proteins)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 83869-56-1 (Granulocyte-Macrophage Colony-Stimulating Factor)
SB  - IM
MH  - Adult
MH  - Biopsy
MH  - Carcinoembryonic Antigen/blood
MH  - Cell Count
MH  - Colonic Neoplasms/blood
MH  - Colony-Forming Units Assay
MH  - Drug Therapy, Combination
MH  - Female
MH  - Flow Cytometry
MH  - Granulocyte-Macrophage Colony-Stimulating Factor/*therapeutic use
MH  - Humans
MH  - Langerhans Cells/*drug effects
MH  - Leukocyte Count
MH  - Leukocytes, Mononuclear/drug effects/physiology
MH  - Male
MH  - Middle Aged
MH  - Neoplasms/drug therapy/*pathology
MH  - Recombinant Proteins/therapeutic use
MH  - Skin/pathology
MH  - Thrombocytopenia/chemically induced
MH  - Tumor Necrosis Factor-alpha/*therapeutic use
OTO - NASA
OT  - Non-programmatic
EDAT- 1999/12/22 00:00
MHDA- 1999/12/22 00:01
CRDT- 1999/12/22 00:00
PHST- 1999/12/22 00:00 [pubmed]
PHST- 1999/12/22 00:01 [medline]
PHST- 1999/12/22 00:00 [entrez]
AID - S1521-6616(99)94778-2 [pii]
AID - 10.1006/clim.1999.4778 [doi]
PST - ppublish
SO  - Clin Immunol. 1999 Dec;93(3):209-21. doi: 10.1006/clim.1999.4778.