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

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 () and In-San Kim ()
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Gi-Hoon Nam: Korea University
Eun Jung Lee: Korea Institute Science and Technology (KIST)
Yoon Kyoung Kim: Korea University
Yeonsun Hong: Korea University
Yoonjeong Choi: Korea University
Myung-Jeom Ryu: Korea Institute Science and Technology (KIST)
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
Seung-Yoon Park: Korea Institute Science and Technology (KIST)
In-San Kim: Korea University

Nature Communications, 2018, vol. 9, issue 1, 1-15

Abstract: 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.

Date: 2018
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DOI: 10.1038/s41467-018-04607-9

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