PMID- 15987427
OWN - NLM
STAT- MEDLINE
DCOM- 20060125
LR  - 20211103
IS  - 1465-542X (Electronic)
IS  - 1465-5411 (Print)
IS  - 1465-5411 (Linking)
VI  - 7
IP  - 3
DP  - 2005
TI  - Dendritic cells are defective in breast cancer patients: a potential role for 
      polyamine in this immunodeficiency.
PG  - R326-35
AB  - INTRODUCTION: Dendritic cells (DCs) are antigen-presenting cells that are 
      currently employed in cancer clinical trials. However, it is not clear whether 
      their ability to induce tumour-specific immune responses when they are isolated 
      from cancer patients is reduced relative to their ability in vivo. We determined 
      the phenotype and functional activity of DCs from cancer patients and 
      investigated the effect of putrescine, a polyamine molecule that is released in 
      large amounts by cancer cells and has been implicated in metastatic invasion, on 
      DCs. METHODS: The IL-4/GM-CSF (granulocyte-macrophage colony-stimulating factor) 
      procedure for culturing blood monocyte-derived DCs was applied to cells from 
      healthy donors and patients (17 with breast, 7 with colorectal and 10 with renal 
      cell carcinoma). The same peroxide-treated tumour cells (M74 cell line) were used 
      for DC pulsing. We investigated the effects of stimulation of autologous 
      lymphocytes by DCs pulsed with treated tumour cells (DC-Tu), and cytolytic 
      activity of T cells was determined in the same target cells. RESULTS: Certain 
      differences were observed between donors and breast cancer patients. The yield of 
      DCs was dramatically weaker, and expression of MHC class II was lower and the 
      percentage of HLA-DR-Lin- cells higher in patients. Whatever combination of 
      maturating agents was used, expression of markers of mature DCs was significantly 
      lower in patients. Also, DCs from patients exhibited reduced ability to stimulate 
      cytotoxic T lymphocytes. After DC-Tu stimulation, specific cytolytic activity was 
      enhanced by up to 40% when DCs were from donors but only up to 10% when they were 
      from patients. IFN-gamma production was repeatedly found to be enhanced in donors 
      but not in patients. By adding putrescine to DCs from donors, it was possible to 
      enhance the HLA-DR-Lin- cell percentage and to reduce the final cytolytic 
      activity of lymphocytes after DC-Tu stimulation, mimicking defective DC function. 
      These putrescine-induced deficiencies were reversed by treating DCs with 
      all-trans retinoic acid. CONCLUSION: These data are consistent with blockade of 
      antigen-presenting cells at an early stage of differentiation in patients with 
      breast cancer. Putrescine released in the microenvironmement of DCs could be 
      involved in this blockade. Use of all-trans retinoic acid treatment to reverse 
      this blockade and favour ex vivo expansion of antigen-specific T lymphocytes is 
      of real interest.
FAU - Gervais, Alban
AU  - Gervais A
AD  - Groupe de Recherche en Therapeutique AntiCancereuse, UPRES 2261, Faculte de 
      Medecine de Rennes, Rennes, France. alban.gervais@wanadoo.fr
FAU - Leveque, Jean
AU  - Leveque J
FAU - Bouet-Toussaint, Francoise
AU  - Bouet-Toussaint F
FAU - Burtin, Florence
AU  - Burtin F
FAU - Lesimple, Thierry
AU  - Lesimple T
FAU - Sulpice, Laurent
AU  - Sulpice L
FAU - Patard, Jean-Jacques
AU  - Patard JJ
FAU - Genetet, Noelle
AU  - Genetet N
FAU - Catros-Quemener, Veronique
AU  - Catros-Quemener V
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20050225
PL  - England
TA  - Breast Cancer Res
JT  - Breast cancer research : BCR
JID - 100927353
RN  - 0 (Antineoplastic Agents)
RN  - 5688UTC01R (Tretinoin)
RN  - V10TVZ52E4 (Putrescine)
SB  - IM
MH  - Aged
MH  - Antineoplastic Agents/pharmacology
MH  - Breast Neoplasms/*immunology
MH  - Carcinoma, Ductal, Breast/*immunology
MH  - Carcinoma, Intraductal, Noninfiltrating/*immunology
MH  - Carcinoma, Lobular/*immunology
MH  - Carcinoma, Renal Cell/immunology
MH  - Cell Transformation, Neoplastic
MH  - Colorectal Neoplasms/immunology
MH  - Dendritic Cells/*immunology
MH  - Female
MH  - Humans
MH  - Kidney Neoplasms/immunology
MH  - Middle Aged
MH  - Phenotype
MH  - Putrescine/*pharmacology
MH  - T-Lymphocytes/physiology
MH  - Tretinoin/pharmacology
PMC - PMC1143555
EDAT- 2005/07/01 09:00
MHDA- 2006/01/26 09:00
PMCR- 2005/02/25
CRDT- 2005/07/01 09:00
PHST- 2004/08/11 00:00 [received]
PHST- 2004/11/26 00:00 [revised]
PHST- 2005/01/18 00:00 [accepted]
PHST- 2005/07/01 09:00 [pubmed]
PHST- 2006/01/26 09:00 [medline]
PHST- 2005/07/01 09:00 [entrez]
PHST- 2005/02/25 00:00 [pmc-release]
AID - bcr1001 [pii]
AID - 10.1186/bcr1001 [doi]
PST - ppublish
SO  - Breast Cancer Res. 2005;7(3):R326-35. doi: 10.1186/bcr1001. Epub 2005 Feb 25.