The Journal of Immunology, 2004, 172: 2727-2728.
Copyright © 2004 by The American Association of Immunologists
Dendritic Cell Activation Kinetics and Cancer Immunotherapy
Matteo Bellone,
Annalisa Camporeale and
Andrea Boni
Cancer Immunotherapy and Gene Therapy Program, Istituto Scientifico H San Raffaele, Milan, Italy
In a recent paper published in The Journal of Immunology, Watanabe and colleagues (1) report on the impact of dendritic cell (DC) activation kinetics on the in vivo priming of Ag-specific T lymphocytes. Thus, the authors focus on a central issue in DC-based immunotherapy, which has already been addressed both in vitro (2, 3) and in vivo (4), reaching very similar conclusions. Worthy of note, Watanabe and colleagues (1) show that as early as 3 h after anti-CD40 Ab stimulation, DCs already developed into powerful cellular vaccines. We found that DCs produced IL-12 and marginally up-regulated cell surface molecules as early as 15 min after exposure to promaturation stimuli, but as for human DCs (2) the peak of IL-12 producing DCs was reached at 8 h, whereas MHC and costimulatory molecules expression significantly increased only later on (4). Unfortunately neither we (4) or Watanabe and colleagues (1) compared the therapeutic efficacy of 3-h and 8-h DCs. Nonetheless, those data strengthen the conclusion that recently activated DCs (i.e., DCs exposed to maturation stimuli for 
8 h) or even immature DCs injected into adjuvant-conditioned skin (5, 6) are to be preferred to fully matured DCs (i.e., DCs exposed to maturation stimuli for 
24 h). Considering that most of the published DC-based vaccination protocols in humans made use of either immature DCs or DCs exposed to promaturation stimuli 24 h (7), the findings described above suggest that clinicians should revise the schedule for DC activation before in vivo injection.
References
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