Polarized type-1 dendritic cells (DC1) producing high levels of IL-12 family members rescue patient TH1-type antimelanoma CD4+ T cell responses in vitro
Polarized type-1 dendritic cells (DC1) producing high levels of IL-12 family members rescue patient TH1-type antimelanoma CD4+ T cell responses in vitro
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DOI：
10.1097/01.cji.0000211316.15278.6e
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发表时间：
2007-01-01
影响因子：
3.9
通讯作者：
Storkus, Walter J.
中科院分区：
文献类型：
--
作者：
Wesa, Amy;Kalinski, Pawel;Storkus, Walter J.
Deficiencies in T(H)1-type immunity in patients with cancer may facilitate tumor progression and limit the effectiveness of current immunotherapy approaches. We hypothesized that Type-1 polarized dendritic cells (DC1) might be able to recondition patient antitumor CD4(+) T cell responses toward the T(H)1-type in vitro. Although DC1 have been previously demonstrated to prime T(H)1 responses from naive CD4+ T cells, their impact on antigen-experienced T-H responses remains unknown. We confirmed our own earlier observations that patient CD4(+) T cell reactivity against melanoma-associated antigens (MAA) was weaker and less Type-I-polarized than their corresponding antiviral responses. Stimulation of patient CD4+ T cells with peptide-pulsed DO (producing multiple IL-12 family member cytokines, including IL-12p70, IL-23, and IL-27) promoted robust T(H)1-type, epitope-specific T cell responses. Addition of exogenous IL-12 family member cytokines alone, or in combination, to nonpolarized DC was insufficient to equate to the benefits associated with DC1-based stimulation; however, IL-27 and IL-12p70 blockade neutralized the ability of DC1 cells to enhance T(H)1-type antitumor immunity in vitro. Notably, DC1-based stimulation seemed capable of "revitalizing" defective T(H)1-type responses within the CD45RC(+) subset of antigen-experienced CD4+ T cells in melanoma patients. In addition to promoting elevated levels of IFN-gamma from responder CD4(+) T cells, DC1-based stimulation also led to increased levels of IL-12R beta 2 and t-bet expression by T-H cells. These results suggest that preexisting CD4(+) T cell immunity to cancer is not relegated to Type-l insufficiency and may be corrected via the application of DC1-based vaccination protocols.
