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.
Nat Commun. 2018 Jun 4;9(1):2165. doi: 10.1038/s41467-018-04607-9.
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.
T 细胞免疫应答的激活对于癌症免疫疗法的治疗效果至关重要。目前的免疫疗法已经在几种癌症的治疗中取得了显著的临床成功；然而，显著的反应仍然局限于少数患者。在这里，我们展示了一种治疗策略，该策略将增强抗原呈递细胞的吞噬活性与免疫原性细胞死亡相结合，以触发有效的抗肿瘤免疫。Rho 激酶 (ROCK) 阻断通过增强树突状细胞 (DC) 对 T 细胞的初始激活，增加癌细胞的吞噬作用并诱导抗肿瘤免疫，从而抑制同种异体肿瘤模型中的肿瘤生长。ROCK 阻断与免疫原性化疗相结合，导致 DC 成熟增加，并协同 CD8 细胞毒性 T 细胞的初始激活和浸润到肿瘤中。这种治疗策略在遗传的鼠乳腺病毒/neu 肿瘤模型中有效抑制肿瘤生长并提高整体存活率。总之，这些结果表明，利用免疫原性杀伤和增强的吞噬作用来增强内在的癌症免疫是癌症免疫治疗的一种有前途的治疗策略。
