PMID- 12839960
OWN - NLM
STAT- MEDLINE
DCOM- 20030825
LR  - 20201215
IS  - 0008-5472 (Print)
IS  - 0008-5472 (Linking)
VI  - 63
IP  - 13
DP  - 2003 Jul 1
TI  - Critical impact of the kinetics of dendritic cells activation on the in vivo 
      induction of tumor-specific T lymphocytes.
PG  - 3688-94
AB  - Dendritic cells (DCs) need activation for the priming of antigen-specific immune 
      responses. Recently activated DCs were described to prime in vitro strong T 
      helper cell type 1 (Th(1)) responses, whereas at later time points, the same 
      cells preferentially prime Th(2) cells [Langenkemp, A. et al., Nat. Immunol. 1: 
      311-316, 2000]. Because the immune response against cancer strongly depends on 
      CTLs of Th(1)-like phenotype (Tc(1)), we verified here whether the kinetics of 
      DCs activation also impacted on in vivo priming of tumor-specific CTLs. After 
      pulsing with the CTL epitope TRP-2(180-188), bone-marrow-derived DCs, exposed to 
      lipopolysaccharide (LPS) for 8 h (8hDC), elicited a more powerful Tc(1) response 
      in C57BL/6 mice than did untreated DCs, or DCs exposed to LPS for 48 h (48hDC). 
      Indeed, 8hDCs were the most potent protective and therapeutic vaccine against B16 
      melanoma. Despite a higher expression of MHC and costimulatory molecules by 
      48hDCs, 8hDCs and 48hDCs showed comparable allostimulatory and migration 
      potential, and susceptibility to CTL-mediated apoptosis. However, 8hDCs exhibited 
      a significantly higher interleukin (IL)-12 production potential. Release of IL-12 
      was necessary to induce potent Tc(1) cells, because DCs from IL-12p40(-/-) mice, 
      irrespective of their maturation level, generated low CTL responses, comparable 
      with 48hDCs and 0hDCs from wild-type animals. Our data are relevant for the 
      design of DC-based vaccines.
FAU - Camporeale, Annalisa
AU  - Camporeale A
AD  - Cancer Immunotherapy and Gene Therapy Program, Istituto Scientifico H San 
      Raffaele, 20132 Milan, Italy.
FAU - Boni, Andrea
AU  - Boni A
FAU - Iezzi, Giandomenica
AU  - Iezzi G
FAU - Degl'Innocenti, Elena
AU  - Degl'Innocenti E
FAU - Grioni, Matteo
AU  - Grioni M
FAU - Mondino, Anna
AU  - Mondino A
FAU - Bellone, Matteo
AU  - Bellone M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Cancer Res
JT  - Cancer research
JID - 2984705R
RN  - 187348-17-0 (Interleukin-12)
SB  - IM
MH  - Animals
MH  - Apoptosis/immunology
MH  - Bone Marrow Cells/cytology/immunology
MH  - *Cytotoxicity, Immunologic
MH  - Dendritic Cells/*immunology/pathology
MH  - Female
MH  - Immunization
MH  - Immunophenotyping
MH  - Interleukin-12/deficiency/immunology
MH  - Kinetics
MH  - Lymphocyte Activation/*immunology
MH  - Melanoma, Experimental/*immunology/pathology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - T-Lymphocytes/*immunology/pathology
MH  - Th1 Cells/immunology
MH  - Th2 Cells/immunology
EDAT- 2003/07/04 05:00
MHDA- 2003/08/26 05:00
CRDT- 2003/07/04 05:00
PHST- 2003/07/04 05:00 [pubmed]
PHST- 2003/08/26 05:00 [medline]
PHST- 2003/07/04 05:00 [entrez]
PST - ppublish
SO  - Cancer Res. 2003 Jul 1;63(13):3688-94.