PMID- 18317362
OWN - NLM
STAT- MEDLINE
DCOM- 20080819
LR  - 20201212
IS  - 1524-9557 (Print)
IS  - 1524-9557 (Linking)
VI  - 31
IP  - 3
DP  - 2008 Apr
TI  - Interferon-alpha (IFN-alpha)-conditioned DC preferentially stimulate type-1 and 
      limit Treg-type in vitro T-cell responses from RCC patients.
PG  - 254-62
LID - 10.1097/CJI.0b013e318167b023 [doi]
AB  - Dendritic cells (DCs) are potent antigen presenting cells and represent 
      attractive candidates for use in novel immunotherapies for patients with renal 
      cell carcinoma (RCC), a disease that has proven refractory to conventional 
      treatment modalities, such as chemotherapy and radiotherapy. Given the perceived 
      need to augment antitumor type-1 immunity (TC1 and Th1) as a therapeutic end 
      point, and the known functional plasticity of DC populations that may display 
      heterogeneous capacity to promote T-cell responses, we sought to identify a 
      preferred DC preparation with this capacity. We compared 2 different preparations 
      of monocyte-derived DC using interferon-alpha (IFN-alpha) (IFN-DC and alphaDC1) 
      with classic DCs "matured" (mDCs) using interleukin-1beta/interleukin-6/tumor 
      necrosis factor-alpha/prostaglandin E2, for their ability to promote autologous 
      TC1 antitumor responses from RCC patients in vitro. IFN-alpha-conditioned DC 
      promoted significantly higher numbers of RCC-specific CD8+ T cells exhibiting a 
      cytotoxic phenotype after in vitro stimulation (IVS) than cytokine cocktail-mDCs. 
      Furthermore, IVS using IFN-DCs was able to diminish regulatory-type T cells among 
      CD4+ T-cell responder populations versus IVS using conventional mDC-based 
      vaccines. These data emphasize an important role for IFN-alpha in modulating the 
      immunologic functions of DCs toward a polarized DC1-type capable of coordinately 
      promoting TH1-type and TC1-type T-cell mediated immunity and supports the 
      translational development of patient-derived IFN-alpha-conditioned DC for use in 
      novel immunotherapies for patients with RCC, and in whom, endogenous 
      tumor-specific TC1 effector cells may be dysfunctional, anergic, or prone to 
      undergo apoptosis.
FAU - Gigante, Margherita
AU  - Gigante M
AD  - Department of Biomedical Sciences, University of Foggia, Foggia, Italy.
FAU - Mandic, Maja
AU  - Mandic M
FAU - Wesa, Amy K
AU  - Wesa AK
FAU - Cavalcanti, Elisabetta
AU  - Cavalcanti E
FAU - Dambrosio, Michele
AU  - Dambrosio M
FAU - Mancini, Vito
AU  - Mancini V
FAU - Battaglia, Michele
AU  - Battaglia M
FAU - Gesualdo, Loreto
AU  - Gesualdo L
FAU - Storkus, Walter J
AU  - Storkus WJ
FAU - Ranieri, Elena
AU  - Ranieri E
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Immunother
JT  - Journal of immunotherapy (Hagerstown, Md. : 1997)
JID - 9706083
RN  - 0 (Cytokines)
RN  - 0 (Interferon Type I)
RN  - 0 (Interferon-alpha)
RN  - 0 (Recombinant Proteins)
RN  - 82115-62-6 (Interferon-gamma)
SB  - IM
MH  - Carcinoma, Renal Cell/blood/*immunology/pathology
MH  - Cell Communication
MH  - Cell Differentiation/drug effects/immunology
MH  - Cells, Cultured
MH  - Cytokines/immunology
MH  - Cytotoxicity, Immunologic
MH  - Dendritic Cells/*immunology/pathology
MH  - Humans
MH  - Immunologic Memory
MH  - Immunotherapy, Active
MH  - Interferon Type I/immunology/pharmacology
MH  - Interferon-alpha/*immunology/metabolism/pharmacology
MH  - Interferon-gamma/immunology
MH  - Kidney Neoplasms/blood/*immunology/pathology
MH  - *Lymphocyte Activation/drug effects
MH  - Recombinant Proteins
MH  - T-Lymphocytes, Regulatory/*immunology
MH  - Th1 Cells/*immunology
EDAT- 2008/03/05 09:00
MHDA- 2008/08/20 09:00
CRDT- 2008/03/05 09:00
PHST- 2008/03/05 09:00 [pubmed]
PHST- 2008/08/20 09:00 [medline]
PHST- 2008/03/05 09:00 [entrez]
AID - 00002371-200804000-00004 [pii]
AID - 10.1097/CJI.0b013e318167b023 [doi]
PST - ppublish
SO  - J Immunother. 2008 Apr;31(3):254-62. doi: 10.1097/CJI.0b013e318167b023.