PMID- 12941846
OWN - NLM
STAT- MEDLINE
DCOM- 20030924
LR  - 20181130
IS  - 0008-5472 (Print)
IS  - 0008-5472 (Linking)
VI  - 63
IP  - 16
DP  - 2003 Aug 15
TI  - The differential influence of allogeneic tumor cell death via DNA damage on 
      dendritic cell maturation and antigen presentation.
PG  - 5143-50
AB  - Dendritic cells (DCs) respond to danger signals from tissue injury by amplifying 
      their immune-inducing capacity. In the cancer context, this may lead to in vivo 
      antitumor synergism between DCs and DNA-damaging chemotherapeutic agents. Neither 
      the interaction between DCs and dying tumor cells nor whether different ways of 
      inducing cell injury can deliver danger signals of different strength to DCs nor 
      the potential role of damaged DNA as a danger signal has been studied rigorously. 
      Here we report that coculture of immature DCs with tumor cells treated with the 
      alkylating agents melphalan and chlorambucil leads to enhanced autologous and 
      allogeneic T-cell activation, up-regulation of surface expression of MHC and 
      costimulatory molecules, and increased interleukin (IL)-12 secretion. Exposure of 
      the same DCs to tumor cells killed by cytarabine or by freeze-thaw (primary 
      necrosis) resulted in significantly less T-cell proliferation and IL-12 
      production, indicating that DCs are able to sense and respond differentially to 
      the mode of cell death. Exposure of DCs to DNA purified from tumor cells treated 
      with alkylating agents also increased their T-cell-stimulating capacity, 
      expression of CD86, and IL-12 secretion, supporting the hypothesis that the 
      activating effects of tumor cells are linked to the nature of the DNA damage. 
      This is the first study that shows that DCs respond differentially to killed 
      tumor cells, depending upon the mechanism of DNA damage and consequent cell 
      death.
FAU - Rad, Ariel N
AU  - Rad AN
AD  - Department of Immunology, Windeyer Institute of Medical Sciences, University 
      College London, London W1T 4JF, United Kingdom.
FAU - Pollara, Gabriele
AU  - Pollara G
FAU - Sohaib, S M Afzal
AU  - Sohaib SM
FAU - Chiang, Cheryl
AU  - Chiang C
FAU - Chain, Benjamin M
AU  - Chain BM
FAU - Katz, David R
AU  - Katz DR
LA  - eng
GR  - CA88567/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Cancer Res
JT  - Cancer research
JID - 2984705R
RN  - 0 (Antigens, CD)
RN  - 0 (Antineoplastic Agents, Alkylating)
RN  - 0 (B7-2 Antigen)
RN  - 0 (CD86 protein, human)
RN  - 0 (Membrane Glycoproteins)
RN  - 187348-17-0 (Interleukin-12)
SB  - IM
MH  - *Antigen Presentation
MH  - Antigens, CD/analysis
MH  - Antineoplastic Agents, Alkylating/pharmacology
MH  - B7-2 Antigen
MH  - Cell Death
MH  - Coculture Techniques
MH  - *DNA Damage
MH  - Dendritic Cells/*physiology
MH  - Humans
MH  - Interleukin-12/metabolism
MH  - Lymphocyte Activation
MH  - Membrane Glycoproteins/analysis
MH  - Neoplasms/*drug therapy/immunology/pathology
MH  - T-Lymphocytes/immunology
MH  - U937 Cells
MH  - Up-Regulation
EDAT- 2003/08/28 05:00
MHDA- 2003/09/25 05:00
CRDT- 2003/08/28 05:00
PHST- 2003/08/28 05:00 [pubmed]
PHST- 2003/09/25 05:00 [medline]
PHST- 2003/08/28 05:00 [entrez]
PST - ppublish
SO  - Cancer Res. 2003 Aug 15;63(16):5143-50.