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, In-San Kim

Research output: Contribution to journalArticle

10 Citations (Scopus)

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.

Original languageEnglish
Article number2165
JournalNature Communications
Volume9
Issue number1
DOIs
Publication statusPublished - 2018 Dec 1

Fingerprint

rho-Associated Kinases
immunity
Cell death
death
Tumors
Immunity
Cell Death
tumors
actuators
cancer
T-cells
priming
Neoplasms
Immunotherapy
cells
T-Lymphocytes
Chemotherapy
Dendritic Cells
viruses
antigens

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Cite this

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

In: Nature Communications, Vol. 9, No. 1, 2165, 01.12.2018.

Research output: Contribution to journalArticle

Nam, GH, Lee, EJ, Kim, YK, Hong, Y, Choi, Y, Ryu, MJ, Woo, J, Cho, Y, Ahn, DJ, Yang, Y, Kwon, IC, Park, SY & Kim, I-S 2018, 'Combined Rho-kinase inhibition and immunogenic cell death triggers and propagates immunity against cancer', Nature Communications, vol. 9, no. 1, 2165. https://doi.org/10.1038/s41467-018-04607-9
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. / Combined Rho-kinase inhibition and immunogenic cell death triggers and propagates immunity against cancer. In: Nature Communications. 2018 ; Vol. 9, No. 1.
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