Nam et al. show that blockade of Rho-associated kinases (ROCKs) using ROCK inhibitor Y27632 increased phagocytosis of tumor cells in vitro and in mice with syngeneic tumors. In vivo, ROCK inhibition led to increased migratory CD103+ DC-mediated CD8+ T cell priming, IFNγ production, and tumor growth suppression. Combination of doxorubicin and Y27632 increased infiltration of CD8+ T cells into the tumor and further suppressed tumor growth, leading to increased survival, complete tumor regression, and long term memory in some mice bearing syngeneic or autochthonous tumors.
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.
Author Info: (1) KU-KIST Graduate School of Converging Science and Technology, Korea University, Seoul, 02841, Republic of Korea. Center for Theragnosis, Biomedical Research Institute, Korea In
Author Info: (1) KU-KIST Graduate School of Converging Science and Technology, Korea University, Seoul, 02841, Republic of Korea. Center for Theragnosis, Biomedical Research Institute, Korea Institute Science and Technology (KIST), Seoul, 02792, Republic of Korea. (2) Center for Theragnosis, Biomedical Research Institute, Korea Institute Science and Technology (KIST), Seoul, 02792, Republic of Korea. Department of Chemical Engineering, School of Applied Chemical Engineering, Kyungpook National University, Daegu, 41566, Republic of Korea. (3) KU-KIST Graduate School of Converging Science and Technology, Korea University, Seoul, 02841, Republic of Korea. Center for Theragnosis, Biomedical Research Institute, Korea Institute Science and Technology (KIST), Seoul, 02792, Republic of Korea. (4) KU-KIST Graduate School of Converging Science and Technology, Korea University, Seoul, 02841, Republic of Korea. Center for Theragnosis, Biomedical Research Institute, Korea Institute Science and Technology (KIST), Seoul, 02792, Republic of Korea. (5) KU-KIST Graduate School of Converging Science and Technology, Korea University, Seoul, 02841, Republic of Korea. Center for Theragnosis, Biomedical Research Institute, Korea Institute Science and Technology (KIST), Seoul, 02792, Republic of Korea. (6) Center for Theragnosis, Biomedical Research Institute, Korea Institute Science and Technology (KIST), Seoul, 02792, Republic of Korea. College of Medicine, Yonsei University, Seoul, 120-752, Republic of Korea. (7) Research Animal Resource Center, Korea Institute of Science and Technology (KIST), Seoul, 02792, Republic of Korea. (8) Research Animal Resource Center, Korea Institute of Science and Technology (KIST), Seoul, 02792, Republic of Korea. (9) KU-KIST Graduate School of Converging Science and Technology, Korea University, Seoul, 02841, Republic of Korea. (10) Center for Theragnosis, Biomedical Research Institute, Korea Institute Science and Technology (KIST), Seoul, 02792, Republic of Korea. (11) KU-KIST Graduate School of Converging Science and Technology, Korea University, Seoul, 02841, Republic of Korea. Center for Theragnosis, Biomedical Research Institute, Korea Institute Science and Technology (KIST), Seoul, 02792, Republic of Korea. (12) Center for Theragnosis, Biomedical Research Institute, Korea Institute Science and Technology (KIST), Seoul, 02792, Republic of Korea. psyoon@dongguk.ac.kr. Department of Biochemistry, School of Medicine, Dongguk University, Gyeongju, 38066, Republic of Korea. psyoon@dongguk.ac.kr. (13) KU-KIST Graduate School of Converging Science and Technology, Korea University, Seoul, 02841, Republic of Korea. iskim14@kist.re.kr. Center for Theragnosis, Biomedical Research Institute, Korea Institute Science and Technology (KIST), Seoul, 02792, Republic of Korea. iskim14@kist.re.kr.
