Intranodal injection of semimature monocyte-derived dendritic cells induces T helper type 1 responses to protein neoantigen
Dendritic cells (DCs) represent the most potent antigen-presenting cells of the immune system capable of initiating primary immune responses to neoantigens. Here we characterize the primary CD4 T-cell immune response to protein keyhole limpet hemocyanin (KLH) in 5 metastatic melanoma patients underg...
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| Main Authors: | , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
January 30, 2003
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| In: |
Blood
Year: 2003, Volume: 102, Issue: 1, Pages: 36-42 |
| ISSN: | 1528-0020 |
| DOI: | 10.1182/blood-2002-07-2274 |
| Online Access: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1182/blood-2002-07-2274 Verlag, lizenzpflichtig, Volltext: https://ashpublications.org/blood/article/102/1/36/16789/Intranodal-injection-of-semimature-monocyte 
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| Author Notes: | Michel Gilliet, Martin Kleinhans, Erica Lantelme, Dirk Schadendorf, Günter Burg, and Frank O. Nestle |
| Summary: | Dendritic cells (DCs) represent the most potent antigen-presenting cells of the immune system capable of initiating primary immune responses to neoantigens. Here we characterize the primary CD4 T-cell immune response to protein keyhole limpet hemocyanin (KLH) in 5 metastatic melanoma patients undergoing a tumor peptide–based dendritic cell vaccination trial. Monocyte-derived dendritic cells displaying a semimature phenotype, as defined by surface markers, were loaded ex vivo with antigen and injected intranodally at weekly intervals for 4 weeks. All patients developed a strong and long-lasting delayed-type hypersensitivity reactivity to KLH, which correlated with the induction of KLH-dependent proliferation of CD4 T cells in vitro. Secondary in vitro stimulation with KLH showed significant increase in interferon-γ and interleukin-2 (IL-2) but not IL-4, IL-5, nor IL-10 secretion by bulk T cells. On the single-cell level, most TH1 cells among in vitro–generated KLH-specific T-cell lines confirmed the preferential induction of a KLH-specific type 1 T helper immune response. Furthermore, the induction of KLH-specific antibodies of the IgG2 subtype may reflect the induction of a type 1 cytokine profile in vivo after vaccination. Our results indicate that intranodal vaccination with semimature DCs can prime strong, long-lasting CD4 T-cell responses with a TH1-type cytokine profile in cancer patients. |
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| Item Description: | Gesehen am 18.11.2020 |
| Physical Description: | Online Resource |
| ISSN: | 1528-0020 |
| DOI: | 10.1182/blood-2002-07-2274 |