Combined Rho-kinase inhibition and immunogenic cell death triggers and propagates immunity against cancer
- Authors
- Nam, Gi-Hoon; Lee, Eun Jung; Kim, Yoon Kyoung; Hong, Yeonsun; Choi, Yoonjeong; Ryu, Myung-Jeom; Woo, Jiwan; Cho, Yakdol; Ahn, Dong June; Yang, Yoosoo; Kwon, Ick-Chan; Park, Seung-Yoon; Kim, In-San
- Issue Date
- 4-Jun-2018
- Publisher
- NATURE PUBLISHING GROUP
- Citation
- NATURE COMMUNICATIONS, v.9
- Indexed
- SCIE
SCOPUS
- Journal Title
- NATURE COMMUNICATIONS
- Volume
- 9
- URI
- https://scholar.korea.ac.kr/handle/2021.sw.korea/74965
- DOI
- 10.1038/s41467-018-04607-9
- ISSN
- 2041-1723
- 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.
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- Appears in
Collections - College of Engineering > Department of Chemical and Biological Engineering > 1. Journal Articles
- Graduate School > KU-KIST Graduate School of Converging Science and Technology > 1. Journal Articles
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