Combined Rho-kinase inhibition and immunogenic cell death triggers and propagates immunity against cancer
- Combined Rho-kinase inhibition and immunogenic cell death triggers and propagates immunity against cancer
- 권익찬; 우지완; 김인산; 양유수; 조약돌; 안동준; 남기훈; 최윤정; 홍연선; 김윤경; Eun Jung Lee; Myung-Jeom Ryu; Seung-Yoon Park
- Issue Date
- Nature Communications
- VOL 9, 2165
- 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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