PMID- 14634105
OWN - NLM
STAT- MEDLINE
DCOM- 20040301
LR  - 20210102
IS  - 0022-1767 (Print)
IS  - 0022-1767 (Linking)
VI  - 171
IP  - 11
DP  - 2003 Dec 1
TI  - Dendritic cells charged with apoptotic tumor cells induce long-lived protective 
      CD4+ and CD8+ T cell immunity against B16 melanoma.
PG  - 5940-7
AB  - Dendritic cells (DCs) are potent APCs and attractive vectors for cancer 
      immunotherapy. Using the B16 melanoma, a poorly immunogenic experimental tumor 
      that expresses low levels of MHC class I products, we investigated whether DCs 
      loaded ex vivo with apoptotic tumor cells could elicit combined CD4(+) and CD8(+) 
      T cell dependent, long term immunity following injection into mice. The bone 
      marrow-derived DCs underwent maturation during overnight coculture with apoptotic 
      melanoma cells. Following injection, DCs migrated to the draining lymph nodes 
      comparably to control DCs at a level corresponding to approximately 0.5% of the 
      injected inoculum. Mice vaccinated with tumor-loaded DCs were protected against 
      an intracutaneous challenge with B16, with 80% of the mice remaining tumor-free 
      12 wk after challenge. CD4(+) and CD8(+) T cells were efficiently primed in 
      vaccinated animals, as evidenced by IFN-gamma secretion after in vitro 
      stimulation with DCs loaded with apoptotic B16 or DCs pulsed with the naturally 
      expressed melanoma Ag, tyrosinase-related protein 2. In addition, B16 melanoma 
      cells were recognized by immune CD8(+) T cells in vitro, and cytolytic activity 
      against tyrosinase-related protein 2(180-188)-pulsed target cells was observed in 
      vivo. When either CD4(+) or CD8(+) T cells were depleted at the time of 
      challenge, the protection was completely abrogated. Mice receiving a tumor 
      challenge 10 wk after vaccination were also protected, consistent with the 
      induction of tumor-specific memory. Therefore, DCs loaded with cells undergoing 
      apoptotic death can prime melanoma-specific helper and CTLs and provide long term 
      protection against a poorly immunogenic tumor in mice.
FAU - Goldszmid, Romina S
AU  - Goldszmid RS
AD  - Instituto Leloir, Instituto de Investigaciones Bioquimicas Buenos Aires, 
      Argentina.
FAU - Idoyaga, Juliana
AU  - Idoyaga J
FAU - Bravo, Alicia I
AU  - Bravo AI
FAU - Steinman, Ralph
AU  - Steinman R
FAU - Mordoh, Jose
AU  - Mordoh J
FAU - Wainstok, Rosa
AU  - Wainstok R
LA  - eng
GR  - 5P01CA84512-03/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Immunol
JT  - Journal of immunology (Baltimore, Md. : 1950)
JID - 2985117R
RN  - 0 (Antigens, CD)
RN  - 0 (B7-2 Antigen)
RN  - 0 (Cancer Vaccines)
RN  - 0 (Cd86 protein, mouse)
RN  - 0 (Histocompatibility Antigens Class II)
RN  - 0 (Membrane Glycoproteins)
SB  - IM
MH  - Adoptive Transfer
MH  - Animals
MH  - Antigens, CD/biosynthesis
MH  - Apoptosis/*immunology
MH  - B7-2 Antigen
MH  - CD4-Positive T-Lymphocytes/*immunology
MH  - CD8-Positive T-Lymphocytes/*immunology
MH  - Cancer Vaccines/administration & dosage/immunology
MH  - Cell Line, Tumor
MH  - Cell Movement/immunology
MH  - Cells, Cultured
MH  - Coculture Techniques
MH  - Cytotoxicity, Immunologic/immunology
MH  - Dendritic Cells/immunology/*pathology/*transplantation
MH  - Histocompatibility Antigens Class II/biosynthesis
MH  - Immunity, Cellular
MH  - Immunity, Innate/immunology
MH  - Immunologic Memory/immunology
MH  - Lymph Nodes/immunology/metabolism/pathology
MH  - Male
MH  - Melanoma, Experimental/*immunology/pathology/*prevention & control
MH  - Membrane Glycoproteins/biosynthesis
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Phagocytosis/*immunology
MH  - Up-Regulation/immunology
EDAT- 2003/11/25 05:00
MHDA- 2004/03/03 05:00
CRDT- 2003/11/25 05:00
PHST- 2003/11/25 05:00 [pubmed]
PHST- 2004/03/03 05:00 [medline]
PHST- 2003/11/25 05:00 [entrez]
AID - 10.4049/jimmunol.171.11.5940 [doi]
PST - ppublish
SO  - J Immunol. 2003 Dec 1;171(11):5940-7. doi: 10.4049/jimmunol.171.11.5940.