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Critical Reviews™ in Immunology
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ISSN Online: 2162-6472

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Critical Reviews™ in Immunology

DOI: 10.1615/CritRevImmunol.v21.i1-3.110
22 pages

Diverse Functional Activity of CD83+ Monocyte-Derived Dendritic Cells and the Implications for Cancer Vaccines

Brian J. Czerniecki
Department of Surgery and Harrison Surgical Research Center, University of Pennsylvania, 4th Floor Silverstein, 3400 Spruce Street, Philadelphia, PA 19104
Peter A. Cohen
Center for Surgery Research, NE6-307, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195, USA
Mark B. Faries
John Wayne Cancer Institute, 2200 Santa Monica Blvd, Santa Monica, CA 90404
Shuwen Xu
Department of Surgery and Harrison Surgical Research Center, University of Pennsylvania, 4th Floor Silverstein, 3400 Spruce Street, Philadelphia, PA 19104
James G. Roros
Department of Surgery and Harrison Surgical Research Center, University of Pennsylvania, 4th Floor Silverstein, 3400 Spruce Street, Philadelphia, PA 19104
Isabelle Bedrosian
Department of Surgery and Harrison Surgical Research Center, University of Pennsylvania, 4th Floor Silverstein, 3400 Spruce Street, Philadelphia, PA 19104

ABSTRAKT

Antigen-loaded dendritic cells (DCs) provide key regulatory signals to T cells during a developing antitumor response. In addition to providing costimulation, mature DC provides cytokine and chemokine signals that can define the T1 vs T2 nature of the antitumor T-cell response as well as whether T cells engage in direct interactions with tumor cells. In serum-free culture conditions that hasten the differentiation of monocytes into mature DCs, certain agents, such as CD40L, accelerate phenotypic maturation (e.g., CD83 and costimulatory molecule expression) without influencing the acquisition of Dc1/Dc2 characteristics. In contrast, exposure to serum-free medium and interferon-g (IFN-g) rapidly influences CD83+ DCs to secrete high levels of IL-12, IL-6, and MIP-1b, and promotes Dc1 differentiation. In contrast, CD83+ DCs matured in serum-free medium in the absence of IFN-g, or in the presence of calcium signaling agents, prostaglandin-E2, or IFN-a, produce no IL-12, scant IL-6, and prodigious IL-8, MDC, and TARC, and promote Dc2 differentiation. T cells sensitized via IL-12–secreting, peptide-pulsed DCs secrete cytokines when subsequently exposed to relevant peptide-pulsed antigen-presenting cells (APCs) or to HLA-compatible tumor cells endogenously expressing the peptide. In contrast, T cells sensitized via IL-12 nonsecreting DC were limited to antigenic reactivation through APC contact rather than tumor cell contact. Therefore, the development of antitumor responses can be dramatically influenced not only by costimulation, but also by the cytokine and chemokine production of DCs, which must be considered in the development of cancer vaccines.


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