Hyperthermia Enhances CTL Cross-Priming

Shi, Honglian; Cao, Tinghua; Connolly, John E.; Monnet, Laurence; Bennett, Lynda; Chapel, Sylvie; Bagnis, Claude; Mannoni, P; Davoust, Jean; Palucka, A. Karolina; Banchereau, Jacques

doi:10.4049/jimmunol.176.4.2134

Cited by 93 publications

(80 citation statements)

References 30 publications

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“…Heat-treated tumor cells are an effective source of TAAs for a FC-based vaccine. Our findings are consistent with those of another study demonstrating that the increased transcription and translation of multiple TAAs by heat treatment results in enhanced cross-priming by DCs via up-regulation of both HSPs and TAAs (67). Importantly, OK/HS-FCs are the most potent inducers of TAA-specific polyclonal CTL responses in HLA-A2-and/or A24-restricted manners in this experimental setting.…”

Section: Discussionsupporting

confidence: 81%

Synergistic Induction of Antigen-Specific CTL by Fusions of TLR-Stimulated Dendritic Cells and Heat-Stressed Tumor Cells

Koido

Hara

Homma

et al. 2007

The Journal of Immunology

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Dendritic cell (DC)/tumor cell fusion cells (FCs) can induce potent CTL responses. The therapeutic efficacy of a vaccine requires the improved immunogenicity of both DCs and tumor cells. The DCs stimulated with the TLR agonist penicillin-killed Streptococcus pyogenes (OK-432; OK-DCs) showed higher expression levels of MHC class I and II, CD80, CD86, CD83, IL-12, and heat shock proteins (HSPs) than did immature DCs. Moreover, heat-treated autologous tumor cells displayed a characteristic phenotype with increased expression of HSPs, carcinoembryonic Ag (CEA), MUC1, and MHC class I (HLA-A2 and/or A24). In this study, we have created four types of FC preparation by alternating fusion cell partners: 1) immature DCs fused with unheated tumor cells; 2) immature DCs fused with heat-treated tumor cells; 3) OK-DCs fused with unheated tumor cells; and 4) OK-DCs fused with heat-treated tumor cells. Although OK-DCs fused with unheated tumor cells efficiently enhanced CTL induction, OK-DCs fused with heat-treated tumor cells were most active, as demonstrated by: 1) up-regulation of multiple HSPs, MHC class I and II, CEA, CD80, CD86, CD83, and IL-12; 2) activation of CD4+ and CD8+ T cells able to produce IFN- γ at higher levels; 3) efficient induction of CTL activity specific for CEA or MUC1 or both against autologous tumor; and 4) superior abilities to induce CD107+IFN-γ+CD8+ T cells and CD154+ IFN-γ+CD4+ T cells. These results strongly suggest that synergism between OK-DCs and heat-treated tumor cells enhances the immunogenicity of FCs and provides a promising means of inducing therapeutic antitumor immunity.

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Section: Discussionsupporting

confidence: 81%

Synergistic Induction of Antigen-Specific CTL by Fusions of TLR-Stimulated Dendritic Cells and Heat-Stressed Tumor Cells

Koido

Hara

Homma

et al. 2007

The Journal of Immunology

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“…Immunostimulatory activity of tumor cells enriched in heat shock proteins after induction of hyperthermia has also been observed in some animal models as well as with human cells in culture. [150][151][152] This is also in accordance with murine studies showing that cell surface hsps represent a distinct immunogenic signal (relative to soluble hsps) and promotes the development of autoimmunity. 153,154 Together, the common theme from these independent observations is that the exposure of certain heat shock proteins on the surface of dying cells may be a marker for immunogenic forms of cell death and deliver an activating stimulus to DCs.…”

Section: Implications For Tumor Immunotherapysupporting

confidence: 71%

Interactions of tumor cells with dendritic cells: balancing immunity and tolerance

2007

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“…Following staining with anti-CD1a FITC (DAKO) and anti-CD14 APC (CALTAG) or PE (BD Biosciences) mAb, [61]. Colo829 was rendered to cell death as described previously [35].…”

Section: Preparationmentioning

confidence: 99%

Both Langerhans cells and interstitial DC cross‐present melanoma antigens and efficiently activate antigen‐specific CTL

et al. 2007

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Dendritic cells (DC) have a unique capacity to present external antigens to CD8 + T cells, i.e. cross-presentation. However, it is not fully established whether the ability to crosspresentation is restricted to a unique subset of DC in humans. Here, we show that two major myeloid DC subsets, i.e. Langerhans cells (LC) and interstitial DC (Int-DC), have the ability to cross-present antigens to CD8 + T cells in vitro. LC and Int-DC were obtained from DC generated by culturing human CD34 + -hematopoietic progenitor cells with GM-CSF, FLT3-L, and TNF-a (CD34-DC). Both DC subsets were able to capture necrotic/apoptotic allogeneic melanoma cells and present antigens to CD8 + T cells, resulting in efficient priming of naive CD8 + T cells into CTL capable of killing melanoma cells. Strikingly, a single stimulation with either subset (LC or Int-DC) or total CD34-DC loaded with necrotic/apoptotic melanoma cells was sufficient to activate melanomaspecific memory CD8 + T cells obtained from patients with metastatic melanoma to become effective CTL. Thus, this study provides the rationale to use CD34-DC loaded with necrotic/apoptotic allogeneic melanoma cells in a clinical trial.

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Hyperthermia Enhances CTL Cross-Priming

Cited by 93 publications

References 30 publications

Synergistic Induction of Antigen-Specific CTL by Fusions of TLR-Stimulated Dendritic Cells and Heat-Stressed Tumor Cells

Synergistic Induction of Antigen-Specific CTL by Fusions of TLR-Stimulated Dendritic Cells and Heat-Stressed Tumor Cells

Interactions of tumor cells with dendritic cells: balancing immunity and tolerance

Both Langerhans cells and interstitial DC cross‐present melanoma antigens and efficiently activate antigen‐specific CTL

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