Plasmacytoid dendritic cells from human lung cancer draining lymph nodes induce Tc1 responses

Research output: Contribution to journalArticlepeer-review

33 Citations (Scopus)

Abstract

Dendritic cells (DC) resident in draining lymph nodes (LN) of patients with lung cancer are proposed to have a critical role in stimulating anti-tumor immunity. CpG oligodeoxynucleotides are undergoing clinical trials in patients with lung cancer and are likely to target plasmacytoid-DC. The present study, therefore, investigated the capacity of plasmacytoid-DC from human lung cancer draining LN to respond to CpG for activation of T cell responses relevant to anti-tumor immunity. The phenotype of DC was examined by flow cytometry, and cytokine production by cytometric bead array (CBA) and ELISA. Plasmacytoid-DC, purified by cell sorting, were immature but expressed the toll-like receptor, TLR9. Plasmacytoid-DC responded to the CpG oligodeoxynucleotide, CpG 2216, by production of the proinflammatory cytokines, IFN-alpha and IL-6. DC were cocultured with normal, allogeneic T cells, and cytokine production determined by CBA and immunophenotyping. CpG 2216 enhanced IFN-gamma production and induced intracellular production of IFN-gamma by CD8(+) and CD4(+), granzyme B by CD8(+), and IL-2 by CD4(+) T cells, respectively. Ligation of CD40 on plasmacytoid-DC combined with exposure to CpG 2216 also strongly enhanced IFN-gamma production. There was no significant difference between the responses of plasmacytoid-DC from patients with lung cancer and patients with benign carcinoid tumors with no pathologic LN involvement. These results indicate that plasmacytoid DC from the draining LN of patients with lung cancer effectively induce Tc1 immunity and could, therefore, represent a novel and attractive target for immunotherapeutic intervention.
Original languageEnglish
Pages (from-to)360 - 367
Number of pages8
JournalAmerican Journal of Respiratory Cell and Molecular Biology
Volume36
Issue number3
DOIs
Publication statusPublished - Mar 2007

Keywords

  • CD40 Ligand
  • Cell Separation
  • Dendritic Cells
  • HLA-DR Antigens
  • Humans
  • Interferon Type I
  • Interferon-gamma
  • Lung Neoplasms
  • Lymph Nodes
  • Myeloid Cells
  • Oligonucleotides
  • T-Lymphocyte Subsets
  • T-Lymphocytes, Cytotoxic
  • Th1 Cells
  • Toll-Like Receptor 9

Fingerprint

Dive into the research topics of 'Plasmacytoid dendritic cells from human lung cancer draining lymph nodes induce Tc1 responses'. Together they form a unique fingerprint.

Cite this