PMID- 16417648
OWN - NLM
STAT- MEDLINE
DCOM- 20060321
LR  - 20181113
IS  - 1465-542X (Electronic)
IS  - 1465-5411 (Print)
IS  - 1465-5411 (Linking)
VI  - 8
IP  - 1
DP  - 2006
TI  - Spontaneous apoptosis of blood dendritic cells in patients with breast cancer.
PG  - R5
AB  - INTRODUCTION: Dendritic cells (DCs) are key antigen-presenting cells that play an 
      essential role in initiating and directing cellular and humoral immunity, 
      including anti-tumor responses. Due to their critical role in cancer, induction 
      of DC apoptosis may be one of the central mechanisms used by tumors to evade 
      immune recognition. METHODS: Spontaneous apoptosis of blood DCs (lineage negative 
      HLA-DR positive cells) was assessed in peripheral blood mononuclear cells (PBMCs) 
      using Annexin-V and TUNEL assays immediately after blood collection. The role of 
      tumor products was assessed by culturing cells with supernatants derived from 
      breast cancer cell lines (TDSN) or PBMCs (PBMC-SN, as a control). The capacity of 
      DC stimulation to prevent apoptosis was assessed by incubating DC with 
      inflammatory cytokines, poly I:C, IL-12 or CD40 ligand (CD40L) prior to culture 
      with TDSN. Apoptosis was determined by flow cytometry and microscopy, and Bcl-2 
      expression determined by intracellular staining. RESULTS: In this study we 
      document the presence of a significantly higher proportion of apoptotic 
      (Annexin-V+ and TUNEL+) blood DCs in patients with early stage breast cancer 
      (stage I to II; n = 13) compared to healthy volunteers (n = 15). We examined the 
      role of tumor products in this phenomenon and show that supernatants derived from 
      breast cancer lines induce apoptosis of blood DCs in PBMC cultures. Aiming to 
      identify factors that protect blood DC from apoptosis, we compared a range of 
      clinically available maturation stimuli, including inflammatory cytokines (tumor 
      necrosis factor-alpha, IL-1beta, IL-6 and prostaglandin (PG)E2 as a cytokine 
      cocktail), synthetic double-stranded RNA (poly I:C) and soluble CD40 ligand. 
      Although inflammatory cytokines and poly I:C induced robust phenotypic 
      maturation, they failed to protect blood DCs from apoptosis. In contrast, CD40 
      stimulation induced strong antigen uptake, secretion of IL-12 and protected blood 
      DCs from apoptosis through sustained expression of Bcl-2. Exogenous IL-12 
      provided similar Bcl-2 mediated protection, suggesting that CD40L effect is 
      mediated, at least in part, through IL-12 secretion. CONCLUSION: Cumulatively, 
      our results demonstrate spontaneous apoptosis of blood DCs in patients with 
      breast cancer and confirm that ex vivo conditioning of blood DCs can protect them 
      from tumor-induced apoptosis.
FAU - Pinzon-Charry, Alberto
AU  - Pinzon-Charry A
AD  - Dendritic Cell and Cancer Laboratory, Queensland Institute of Medical Research, 
      Brisbane, Queensland, Australia. albertoP@qimr.edu.au
FAU - Maxwell, Tammy
AU  - Maxwell T
FAU - McGuckin, Michael A
AU  - McGuckin MA
FAU - Schmidt, Chris
AU  - Schmidt C
FAU - Furnival, Colin
AU  - Furnival C
FAU - Lopez, J Alejandro
AU  - Lopez JA
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20051216
PL  - England
TA  - Breast Cancer Res
JT  - Breast cancer research : BCR
JID - 100927353
RN  - 0 (CD40 Antigens)
RN  - 187348-17-0 (Interleukin-12)
SB  - IM
CIN - Breast Cancer Res. 2006;8(1):101. PMID: 16469120
MH  - Adult
MH  - Aged
MH  - *Apoptosis
MH  - Breast Neoplasms/*blood/*physiopathology
MH  - CD40 Antigens
MH  - *Dendritic Cells
MH  - Female
MH  - Flow Cytometry
MH  - Humans
MH  - In Situ Nick-End Labeling
MH  - Interleukin-12/physiology
MH  - Middle Aged
MH  - Phenotype
PMC - PMC1413992
EDAT- 2006/01/19 09:00
MHDA- 2006/03/22 09:00
PMCR- 2005/12/16
CRDT- 2006/01/19 09:00
PHST- 2005/09/03 00:00 [received]
PHST- 2005/10/24 00:00 [revised]
PHST- 2005/11/01 00:00 [accepted]
PHST- 2006/01/19 09:00 [pubmed]
PHST- 2006/03/22 09:00 [medline]
PHST- 2006/01/19 09:00 [entrez]
PHST- 2005/12/16 00:00 [pmc-release]
AID - bcr1361 [pii]
AID - 10.1186/bcr1361 [doi]
PST - ppublish
SO  - Breast Cancer Res. 2006;8(1):R5. doi: 10.1186/bcr1361. Epub 2005 Dec 16.