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OP9-DL1 cell co-culture enhances anti-tumour immunity of mouse bone marrow-derived dendritic cells

Authors

  • Fan Feng,

    Corresponding author
    1. Xijing Hospital of Digestive Diseases, The Fourth Military Medical University, 15 West Changle Road, 710032 Xian, Shaanxi, Peoples Republic of China
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  • Jianjun Yang,

    Corresponding author
    1. Xijing Hospital of Digestive Diseases, The Fourth Military Medical University, 15 West Changle Road, 710032 Xian, Shaanxi, Peoples Republic of China
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  • Liping Tong,

    Corresponding author
    1. Xijing Hospital of Digestive Diseases, The Fourth Military Medical University, 15 West Changle Road, 710032 Xian, Shaanxi, Peoples Republic of China
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  • Shifa Yuan,

    1. Xijing Hospital of Digestive Diseases, The Fourth Military Medical University, 15 West Changle Road, 710032 Xian, Shaanxi, Peoples Republic of China
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  • Yangzi Tian,

    1. Department of Dermatology, Xijing Hospital, The Fourth Military Medical University, 15 West Changle Road, 710032 Xian, Shaanxi, Peoples Republic of China
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  • Liu Hong,

    Corresponding author
    1. Xijing Hospital of Digestive Diseases, The Fourth Military Medical University, 15 West Changle Road, 710032 Xian, Shaanxi, Peoples Republic of China
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  • Weizhong Wang,

    1. Xijing Hospital of Digestive Diseases, The Fourth Military Medical University, 15 West Changle Road, 710032 Xian, Shaanxi, Peoples Republic of China
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  • Hongwei Zhang

    Corresponding author
    1. Xijing Hospital of Digestive Diseases, The Fourth Military Medical University, 15 West Changle Road, 710032 Xian, Shaanxi, Peoples Republic of China
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These authors contributed equally to this work.

To whom correspondence should be addressed (email hongwzh@126.com).

Abstract

DCs (dendritic cells) are the strongest professional APCs (antigen-presenting cells) to initiate immune responses against pathogens, but they are usually incompetent in initiating efficient immune responses in the progress of solid tumours. We have shown that Notch signalling plays a pivotal role in DC-dependent anti-tumour immunity. Compared with the control DCs, OP9-DL1 (Delta-like1) cell co-cultured DCs gained increased tumour suppression activity when inoculated together with tumour cells. This was probably due to the activation of Notch signalling in DCs enhancing their ability to evoke anti-tumour immune responses in solid tumours. Indeed, the OP9-DL1 cell co-cultured DCs expressed higher levels of MHC I, MHC II, CXCR4 (CXC chemokine receptor 4), CCR7 (CC chemokine receptor 7), IL-6 (interleukin 6), IL-12 and TNFα (tumour necrosis factor α), and a lower level of IL-10 than control DCs, resulting in more efficient DC migration and T-cell activation in vivo and in vitro. T-cells stimulated by OP9-DL1 cells co-cultured DCs more efficiently; and were cytotoxic against tumour cells, in contrast with control DCs. These results indicated that up-regulation of Notch signalling in DCs by co-culturing with OP9-DL1 cells enhances DC-dependent anti-tumour immune reactions, making the Notch signalling pathway a target for the establishment of the DC-based anti-tumour immunotherapies.

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