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Combined Rho-kinase inhibition and immunogenic cell death triggers and propagates immunity against cancer

Author

Listed:
  • Gi-Hoon Nam

    (Korea University
    Korea Institute Science and Technology (KIST))

  • Eun Jung Lee

    (Korea Institute Science and Technology (KIST)
    Kyungpook National University)

  • Yoon Kyoung Kim

    (Korea University
    Korea Institute Science and Technology (KIST))

  • Yeonsun Hong

    (Korea University
    Korea Institute Science and Technology (KIST))

  • Yoonjeong Choi

    (Korea University
    Korea Institute Science and Technology (KIST))

  • Myung-Jeom Ryu

    (Korea Institute Science and Technology (KIST)
    Yonsei University)

  • Jiwan Woo

    (Korea Institute of Science and Technology (KIST))

  • Yakdol Cho

    (Korea Institute of Science and Technology (KIST))

  • Dong June Ahn

    (Korea University)

  • Yoosoo Yang

    (Korea Institute Science and Technology (KIST))

  • Ick-Chan Kwon

    (Korea University
    Korea Institute Science and Technology (KIST))

  • Seung-Yoon Park

    (Korea Institute Science and Technology (KIST)
    Dongguk University)

  • In-San Kim

    (Korea University
    Korea Institute Science and Technology (KIST))

Abstract

Activation of T cell immune response is critical for the therapeutic efficacy of cancer immunotherapy. Current immunotherapies have shown remarkable clinical success against several cancers; however, significant responses remain restricted to a minority of patients. Here, we show a therapeutic strategy that combines enhancing the phagocytic activity of antigen-presenting cells with immunogenic cell death to trigger efficient antitumour immunity. Rho-kinase (ROCK) blockade increases cancer cell phagocytosis and induces antitumour immunity through enhancement of T cell priming by dendritic cells (DCs), leading to suppression of tumour growth in syngeneic tumour models. Combining ROCK blockade with immunogenic chemotherapy leads to increased DC maturation and synergistic CD8+ cytotoxic T cell priming and infiltration into tumours. This therapeutic strategy effectively suppresses tumour growth and improves overall survival in a genetic mouse mammary tumour virus/Neu tumour model. Collectively, these results suggest that boosting intrinsic cancer immunity using immunogenic killing and enhanced phagocytosis is a promising therapeutic strategy for cancer immunotherapy.

Suggested Citation

  • Gi-Hoon Nam & Eun Jung Lee & Yoon Kyoung Kim & Yeonsun Hong & Yoonjeong Choi & Myung-Jeom Ryu & Jiwan Woo & Yakdol Cho & Dong June Ahn & Yoosoo Yang & Ick-Chan Kwon & Seung-Yoon Park & In-San Kim, 2018. "Combined Rho-kinase inhibition and immunogenic cell death triggers and propagates immunity against cancer," Nature Communications, Nature, vol. 9(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-04607-9
    DOI: 10.1038/s41467-018-04607-9
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    Cited by:

    1. Davide Esposito & Ila Pant & Yao Shen & Rui F. Qiao & Xiaobao Yang & Yiyang Bai & Jian Jin & Poulikos I. Poulikakos & Stuart A. Aaronson, 2022. "ROCK1 mechano-signaling dependency of human malignancies driven by TEAD/YAP activation," Nature Communications, Nature, vol. 13(1), pages 1-14, December.

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