PMID- 16585547
OWN - NLM
STAT- MEDLINE
DCOM- 20060516
LR  - 20210102
IS  - 0022-1767 (Print)
IS  - 0022-1767 (Linking)
VI  - 176
IP  - 8
DP  - 2006 Apr 15
TI  - Immune complex-loaded dendritic cells are superior to soluble immune complexes as 
      antitumor vaccine.
PG  - 4573-80
AB  - Dendritic cells (DCs) play an important role in the induction of T cell 
      responses. Fc gammaRs, expressed on DCs, facilitate the uptake of complexed Ag, 
      resulting in efficient MHC class I and MHC class II Ag presentation and DC 
      maturation. In the present study, we show that prophylactic immunization with DCs 
      loaded with Ag-IgG immune complexes (ICs) leads to efficient induction of tumor 
      protection in mice. Therapeutic vaccinations strongly delay tumor growth or even 
      prevent tumors from growing out. By depleting CD4+ and CD8+ cell populations 
      before tumor challenge, we identify CD8+ cells as the main effector cells 
      involved in tumor eradication. Importantly, we show that DCs that are preloaded 
      in vitro with ICs are at least 1000-fold more potent than ICs injected directly 
      into mice or DCs loaded with the same amount of noncomplexed protein. The 
      contribution of individual Fc gammaRs to Ag presentation, T cell response 
      induction, and induction of tumor protection was assessed. We show that Fc 
      gammaRI and Fc gammaRIII are capable of enhancing MHC class I-restricted Ag 
      presentation to CD8+ T cells in vitro and that these activating Fc gammaRs on DCs 
      are required for efficient priming of Ag-specific CD8+ cells in vivo and 
      induction of tumor protection. These findings show that targeting ICs via the 
      activating Fc gammaRs to DCs in vitro is superior to direct IC vaccination to 
      induce protective tumor immunity in vivo.
FAU - Schuurhuis, Danita H
AU  - Schuurhuis DH
AD  - Department of Immunohematology and Blood Transfusion, Leiden University Medical 
      Center, The Netherlands.
FAU - van Montfoort, Nadine
AU  - van Montfoort N
FAU - Ioan-Facsinay, Andreea
AU  - Ioan-Facsinay A
FAU - Jiawan, Reshma
AU  - Jiawan R
FAU - Camps, Marcel
AU  - Camps M
FAU - Nouta, Jan
AU  - Nouta J
FAU - Melief, Cornelis J M
AU  - Melief CJ
FAU - Verbeek, J Sjef
AU  - Verbeek JS
FAU - Ossendorp, Ferry
AU  - Ossendorp F
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Immunol
JT  - Journal of immunology (Baltimore, Md. : 1950)
JID - 2985117R
RN  - 0 (Antigen-Antibody Complex)
RN  - 0 (Cancer Vaccines)
RN  - 0 (Receptors, IgG)
RN  - 9006-59-1 (Ovalbumin)
SB  - IM
MH  - Animals
MH  - Antigen Presentation
MH  - Antigen-Antibody Complex/*administration & dosage
MH  - CD4-Positive T-Lymphocytes/immunology
MH  - CD8-Positive T-Lymphocytes/immunology
MH  - Cancer Vaccines/*administration & dosage
MH  - Cell Line, Tumor
MH  - Dendritic Cells/*immunology
MH  - In Vitro Techniques
MH  - Melanoma, Experimental/immunology/therapy
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Ovalbumin/immunology
MH  - Receptors, IgG/deficiency/genetics/metabolism
MH  - Solubility
EDAT- 2006/04/06 09:00
MHDA- 2006/05/17 09:00
CRDT- 2006/04/06 09:00
PHST- 2006/04/06 09:00 [pubmed]
PHST- 2006/05/17 09:00 [medline]
PHST- 2006/04/06 09:00 [entrez]
AID - 176/8/4573 [pii]
AID - 10.4049/jimmunol.176.8.4573 [doi]
PST - ppublish
SO  - J Immunol. 2006 Apr 15;176(8):4573-80. doi: 10.4049/jimmunol.176.8.4573.