Diverse functional activity of CD83+ monocyte-derived dendritic cells and the implications for cancer vaccines

Brian J. Czerniecki, Peter A. Cohen, Mark Faries, Shuwen Xu, James G. Roros, Isabelle Bedrosian

Research output: Contribution to journalArticlepeer-review

38 Scopus citations

Abstract

Antigen-loaded dendritic ceils (DCs) provide key regulatory signals to T ceils 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-γ (IFN-γ) rapidly influences CD83+ DCs to secrete high levels of IL-12, IL-6, and MIP-1β, and promotes Dc1 differentiation. In contrast, CD83+ DCs matured in serum-free medium in the absence of IFN-γ, or in the presence of calcium signaling agents, prostaglandin-E2, or IFN-α 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.

Original languageEnglish (US)
Pages (from-to)157-178
Number of pages22
JournalCritical reviews in immunology
Volume21
Issue number1-3
StatePublished - Oct 23 2001

Keywords

  • CD4 T cells
  • CD8 T cells
  • Chemokines
  • Dc1
  • Dc2
  • Dendritic cells
  • IL-12
  • Interferon-γ
  • Tumor rejection

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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