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 2024-01-19T22:33:04Z 2024-01-19T22:33:04Z 2021-09-03 2018-06 2041-1723 https://pubs.kist.re.kr/handle/201004/121301 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. English Nature Publishing Group Combined Rho-kinase inhibition and immunogenic cell death triggers and propagates immunity against cancer Article 10.1038/s41467-018-04607-9 1 Nature Communications, v.9 Nature Communications 9 Y scie scopus 000434015000003 2-s2.0-85048104118 Multidisciplinary Sciences Science & Technology - Other Topics Article SPONTANEOUS MAMMARY-TUMORS DENDRITIC CELLS CALRETICULIN EXPOSURE ACTIN CYTOSKELETON APOPTOTIC CELLS ACTIVATION ROCK THERAPY CHEMOTHERAPY MACROPHAGES