Xu Hui, Zhao Fengshu, Wu Di, Zhang Yunxia, Bao Xueyang, Shi Fangfang, Cai Yunlang, Dou Jun
Department of Pathogenic Biology and Immunology, School of Medicine, Southeast University, Nanjing 210009, China; Department of Gynecology & Obstetrics, Zhongda Hospital, School of Medicine, Southeast University, Nanjing 210009, China.
Department of Pathogenic Biology and Immunology, School of Medicine, Southeast University, Nanjing 210009, China.
Biomed Pharmacother. 2023 May;161:114547. doi: 10.1016/j.biopha.2023.114547. Epub 2023 Mar 16.
Advanced ovarian cancer (OC) patients have limited benefit from current relevant cytotoxic and targeted therapies following debulking surgery. Therefore, new therapeutic strategies are in urgent need. Immunotherapy has shown great potential in tumor treatment, especially in tumor vaccine development. The study objective was to evaluate the immune effects of cancer stem cells (CSCs) vaccines on OC. The CD44CD117CSCs were isolated from human OC HO8910 and SKOV3 cells using the magnetic cell sorting system; the cancer stem-like cells were selected from murine OC ID8 cell by no-serum formed sphere culture. The CSC vaccines were prepared by freezing and thawing these CSCs, which were then injected into mice followed by challenging the different OC cells. The in vivo antitumor efficacy of CSC immunization revealed the vaccines were capable of significantly provoking immune responses to autologous tumor antigens in vaccinated mice as the mice were found to have markedly inhibited tumor growth, prolonged survival, and decreased CSC counts in OC tissues when compared to mice without the CSC vaccination. The in vitro cytotoxicities of immunocytes toward SKOV3, HO8910 and ID8 cells indicated a significant killing efficacy compared with the controls. However, the antitumor efficacy was remarkably reduced whilst the mucin-1 expression in CSC vaccines was down-regulated by small interfering RNA. Overall, findings from this study provided the evidence that has deepened our understanding of CSC vaccine immunogenicity and anti-OC efficacy, particularly for the role of dominant antigen mucin-1. It is possible to turn the CSC vaccine into an immunotherapeutic approach against ovarian cancer.
晚期卵巢癌（OC）患者在减瘤手术后从目前相关的细胞毒性和靶向治疗中获益有限。因此，迫切需要新的治疗策略。免疫疗法在肿瘤治疗中已显示出巨大潜力，尤其是在肿瘤疫苗开发方面。本研究的目的是评估癌症干细胞（CSC）疫苗对OC的免疫效果。使用磁性细胞分选系统从人OC HO8910和SKOV3细胞中分离出CD44⁺CD117⁺ CSCs；通过无血清成球培养从小鼠OC ID8细胞中筛选出癌症干细胞样细胞。通过冻融这些CSCs制备CSC疫苗，然后将其注射到小鼠体内，随后接种不同的OC细胞。CSC免疫的体内抗肿瘤功效表明，与未接种CSC疫苗的小鼠相比，接种疫苗的小鼠体内的疫苗能够显著激发对自体肿瘤抗原的免疫反应，因为发现这些小鼠的肿瘤生长明显受到抑制，生存期延长，OC组织中的CSC数量减少。免疫细胞对SKOV3、HO8910和ID8细胞的体外细胞毒性表明，与对照组相比具有显著的杀伤效果。然而，当CSC疫苗中的黏蛋白-1表达被小干扰RNA下调时，抗肿瘤功效显著降低。总体而言，本研究结果提供了证据，加深了我们对CSC疫苗免疫原性和抗OC功效的理解，特别是对主要抗原黏蛋白-1的作用。将CSC疫苗转化为一种抗卵巢癌的免疫治疗方法是有可能的。
