Department of Otorhinolaryngology-Head and Neck Surgery, Korea University Anam Hospital, Korea University College of Medicine, Seoul, 02841, Republic of Korea.
KU-KIST Graduate School of Converging Science and Technology, Korea University, Seoul, 02456, Republic of Korea; Center for Theragnosis, Biomedical Research Institute, Korea Institute Science and Technology (KIST), Seoul, 02456, Republic of Korea.
Cancer Lett. 2021 Dec 1;522:198-210. doi: 10.1016/j.canlet.2021.09.029. Epub 2021 Sep 24.
The purpose of this study was to determine whether statins can enhance anticancer effects in head and neck squamous cell carcinoma (HNSCC) when used with cisplatin and act as immunogenic cell death (ICD) inducers that can be used in cancer immunotherapy. Statins alone showed both in vitro and in vivo inhibitory effects against HNSCC, and synergistic antitumor effects were observed when combined with cisplatin in a syngeneic murine HNSCC model. Statins increased calreticulin exposure and endoplasmic reticulum stress-related signals in HNSCC cells. In addition, it was confirmed that statins could activate antigen-presenting cells and tumor-specific CD8 T cells with an increase in their numbers in the tumor tissues and draining lymph nodes, with this effect showing significant improvement following the combination therapy with cisplatin. Moreover, in triple combination with both cisplatin and anti-programmed cell death 1 receptor (anti-PD-1) antibody, statins dramatically induced further tumor eradication and improved the survival of tumor-bearing mice. Taken together, these results demonstrate that statins, administered in combination with anti-PD-1 antibody, could enhance the anticancer effect of cisplatin and potentiate the efficacy of immunotherapy for HNSCC and present a rationale for repurposing statins as an adjuvant immunotherapeutic option for HNSCC.
本研究旨在确定他汀类药物与顺铂联合使用时是否可以增强头颈部鳞状细胞癌（HNSCC）的抗癌作用，并作为免疫原性细胞死亡（ICD）诱导剂用于癌症免疫治疗。他汀类药物单独使用时对 HNSCC 具有体外和体内抑制作用，并且在同种异体小鼠 HNSCC 模型中与顺铂联合使用时观察到协同抗肿瘤作用。他汀类药物增加了 HNSCC 细胞中钙网织蛋白的暴露和内质网应激相关信号。此外，还证实他汀类药物可以激活抗原呈递细胞和肿瘤特异性 CD8 T 细胞，增加肿瘤组织和引流淋巴结中的细胞数量，联合顺铂治疗后这种作用显著改善。此外，与顺铂和抗程序性细胞死亡 1 受体（抗 PD-1）抗体的三联组合中，他汀类药物可显著诱导肿瘤进一步消除，并提高荷瘤小鼠的生存率。综上所述，这些结果表明，他汀类药物与抗 PD-1 抗体联合使用可以增强顺铂的抗癌作用，并增强免疫疗法治疗 HNSCC 的疗效，为将他汀类药物重新用作 HNSCC 的辅助免疫治疗选择提供了依据。
