Gi-Hoon Nam1,2, Eun Jung Lee2,3, Yoon Kyoung Kim1,2, Yeonsun Hong1,2, Yoonjeong Choi1,2, Myung-Jeom Ryu2,4, Jiwan Woo5, Yakdol Cho5, Dong June Ahn1, Yoosoo Yang2, Ick-Chan Kwon1,2, Seung-Yoon Park2,6,* & In-San Kim1,2,*
1 KU-KIST Graduate School of Converging Science and Technology, Korea University, Seoul 02841, Republic of Korea. 2 Center for Theragnosis, Biomedical Research Institute, Korea Institute Science and Technology (KIST), Seoul 02792, Republic of Korea. 3 Department of Chemical Engineering, School of Applied Chemical Engineering, Kyungpook National University, Daegu 41566, Republic of Korea. 4 College of Medicine, Yonsei University, Seoul 120-752, Republic of Korea. 5 Research Animal Resource Center, Korea Institute of Science and Technology (KIST), Seoul 02792, Republic of Korea. 6 Department of Biochemistry, School of Medicine, Dongguk University, Gyeongju 38066, Republic of Korea.
These authors contributed equally: Gi-Hoon Nam, Eun Jung Lee.
*Correspondence and requests for materials should be addressed to S.-Y.P. or to I.-S.K.
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.