DNA array and biological characterization of the impact of the maturation status of mouse dendritic cells on their phenotype and antitumor vaccination efficacy

Zhuang Chen, Scott Dehm, Keith Bonham, Huse Kamencic, Bernie Juurlink, Xueshu Zhang, John R. Gordon, Jim Xiang

Research output: Contribution to journalArticlepeer-review

36 Scopus citations

Abstract

We systematically investigated the impact of the relative maturation levels of dendritic cells (DCs) on their cell surface phenotype, expression of cytokines and chemokines/chemokine receptors (by DNA array and RNase protection analyses), biological activities, and abilities to induce tumor immunity. Mature DCs expressed significantly heightened levels of their antigen-presenting machinery (e.g., CD54, CD80, CD86) and numerous cytokines and chemokines/chemokine receptors (i.e., Flt-3L, G-CSF, IL-1α and -1β, IL-6, IL-12, CCL-2, -3, -4, -5, -17, and -22, MIP-2, and CCR7) and were significantly better at inducing effector T cell responses in vitro. Furthermore, mice vaccinated with tumor peptide-pulsed mature DCs better survived challenge with a weakly immunogenic tumor (8 of 8 survivors) than did mice vaccinated with less mature (3 of 8 survived) or immature (0 of 8 survivors) DCs. Nevertheless, intermediate-maturity DCs expressed substantial levels of Flt-3L, IGF-1, IL-1α and -1β, IL-6, CCL-2, -3, -4, -9/10, -17, and -22, MIP-2, osteopontin, CCR-1, -2, -5, and -7, and CXCR-4. Taken together, our data clearly underscore the critical nature of employing DCs of full maturity for DC-based antitumor vaccination strategies.

Original languageEnglish (US)
Pages (from-to)60-71
Number of pages12
JournalCellular Immunology
Volume214
Issue number1
DOIs
StatePublished - Nov 25 2001

Keywords

  • Antitumor immunity
  • Cytokine profile
  • DNA array
  • Dendritic cell vaccine
  • LPS

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