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Plasmacytoid Dendritic Cells from Human Lung Cancer Draining Lymph Nodes Induce Tc1 Responses

Department of Asthma, Allergy and Respiratory Science, King's College; and Department of Thoracic Surgery, Guy's and St Thomas' NHS Foundation Trust, London, United Kingdom

Correspondence and requests for reprints should be addressed to Alexander Faith, Dept. Asthma, Allergy and Respiratory Science, 5th Floor Thomas Guy House, Guy's Hospital, St Thomas St, London SE1 9RT, UK. E-mail: alex.faith{at}kcl.ac.uk

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- and IL-6. DC were cocultured with normal, allogeneic T cells, and cytokine production determined by CBA and immunophenotyping. CpG 2216 enhanced IFN- production and induced intracellular production of IFN- 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- 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.

Key Words: human lung cancer • dendritic cells • lymph node

CLINICAL RELEVANCE The ability of plasmacytoid dendritic cells to induce anti-tumor T cell responses is unclear. We report that plasmacytoid dendritic cells from lymph nodes of patients with lung cancer stimulate Tc1 responses and may thus represent a target for therapeutic intervention.