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Simultaneous activation of T helper function can augment the potency of dendritic cell-based cancer immunotherapy

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Abstract

Purpose

Simultaneous activation of T helper 1 (Th1) cell function has crucial roles in induction of potent cytotoxic T lymphocyte (CTL) responses in cancer immunotherapy. Here, we investigated whether dendritic cell (DC)-based vaccines loaded with both tumor-associated antigen (TAA)-derived MHC class I and pan-MHC class II peptides could elicit more potent CTL responses through simultaneous activation of Th1 function and reduction in CD4+ regulatory T (Treg) cell proliferation.

Methods

C57BL/6 mice bearing LLC1, a mouse Lewis lung cancer cell line, were subcutaneously administered DCs loaded with both LLC-derived MHC class I (MUT1&2) and LLC-unrelated pan-MHC class II (PADRE) peptides (DC-MUT1&2-PADRE). In assays using samples from advanced lung cancer patients, peripheral blood mononuclear cells were stimulated with autologous DCs loaded with both MUC1 MHC class I and PADRE peptides (DC-MUC1-PADRE) in vitro. Subsequently, TAA-specific CTL responses and the population of CD4+ Treg cells were analyzed.

Results

The population of spleen CD4+ PADRE-specific cells producing interferon-gamma (IFNγ) was significantly increased by DC-MUT1&2-PADRE administration. Vaccinations with DC-MUT1&2-PADRE decreased the population of CD4+ Treg cells in spleen and augmented CTL responses, effectively leading to suppression of tumor growth. In assays with human samples, CD4+ Treg cells were induced less frequently, and MUC1-specific cytotoxicity was enhanced by stimulation with DC-MUC1-PADRE compared with that by stimulation with DC-MUC1 alone.

Conclusions

Simultaneous activation of Th1 function by DCs loaded with both TAA-derived MHC class I and PADRE peptides augments TAA-specific CTL responses while reducing Treg cell proliferation.

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Conflict of interest

We declare that we have no conflict of interest.

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Authors and Affiliations

  1. Department of Surgery, Shiga University of Medical Science, Seta-Tsukinowa, Otsu, Shiga, 520-2192, Japan

    Koji Teramoto, Yasuhiko Ohshio, Takuya Fujita & Jun Hanaoka

  2. Department of Respiratory, Breast and Endocrine Surgery, Kagawa University Faculty of Medicine, 1750-1, Miki-cho, Kita-gun, Kagawa, 761-0793, Japan

    Keiichi Kontani

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  1. Koji Teramoto
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  2. Yasuhiko Ohshio
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  3. Takuya Fujita
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  4. Jun Hanaoka
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  5. Keiichi Kontani
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Correspondence to Koji Teramoto.

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Teramoto, K., Ohshio, Y., Fujita, T. et al. Simultaneous activation of T helper function can augment the potency of dendritic cell-based cancer immunotherapy. J Cancer Res Clin Oncol 139, 861–870 (2013). https://doi.org/10.1007/s00432-013-1394-4

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  • DOI: https://doi.org/10.1007/s00432-013-1394-4

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