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

Title
Combined Rho-kinase inhibition and immunogenic cell death triggers and propagates immunity against cancer
Authors
권익찬우지완김인산양유수조약돌안동준남기훈최윤정홍연선김윤경Eun Jung LeeMyung-Jeom RyuSeung-Yoon Park
Issue Date
2018-06
Publisher
Nature Communications
Citation
VOL 9, 2165
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.
URI
http://pubs.kist.re.kr/handle/201004/68023
ISSN
2041-1723
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