Izadpanah Amirhossein, Mohammadkhani Niloufar, Masoudnia Mina, Ghasemzad Mahsa, Saeedian Arefeh, Mehdizadeh Hamid, Poorebrahim Mansour, Ebrahimi Marzieh
Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran.
Department of Clinical Biochemistry, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Cancer Med. 2023 Sep;12(18):18960-18980. doi: 10.1002/cam4.6520. Epub 2023 Sep 12.
Accumulating data reveals that tumors possess a specialized subset of cancer cells named cancer stem cells (CSCs), responsible for metastasis and recurrence of malignancies, with various properties such as self-renewal, heterogenicity, and capacity for drug resistance. Some signaling pathways or processes like Notch, epithelial to mesenchymal transition (EMT), Hedgehog (Hh), and Wnt, as well as CSCs' surface markers such as CD44, CD123, CD133, and epithelial cell adhesion molecule (EpCAM) have pivotal roles in acquiring CSCs properties. Therefore, targeting CSC-related signaling pathways and surface markers might effectively eradicate tumors and pave the way for cancer survival. Since current treatments such as chemotherapy and radiation therapy cannot eradicate all of the CSCs and tumor relapse may happen following temporary recovery, improving novel and more efficient therapeutic options to combine with current treatments is required. Immunotherapy strategies are the new therapeutic modalities with promising results in targeting CSCs. Here, we review the targeting of CSCs by immunotherapy strategies such as dendritic cell (DC) vaccines, chimeric antigen receptors (CAR)-engineered immune cells, natural killer-cell (NK-cell) therapy, monoclonal antibodies (mAbs), checkpoint inhibitors, and the use of oncolytic viruses (OVs) in pre-clinical and clinical studies. This review will mainly focus on blood malignancies but also describe solid cancers.
越来越多的数据表明，肿瘤拥有一类名为癌症干细胞（CSCs）的特殊癌细胞亚群，它们负责恶性肿瘤的转移和复发，具有自我更新、异质性和耐药性等多种特性。一些信号通路或过程，如Notch、上皮-间质转化（EMT）、刺猬信号通路（Hh）和Wnt，以及CSCs的表面标志物，如CD44、CD123、CD133和上皮细胞粘附分子（EpCAM），在获得CSCs特性方面起着关键作用。因此，靶向与CSCs相关的信号通路和表面标志物可能有效地根除肿瘤，并为癌症患者的生存铺平道路。由于目前的化疗和放疗等治疗方法无法根除所有的CSCs，且肿瘤可能在暂时缓解后复发，因此需要改进新的、更有效的治疗方案并与现有治疗方法相结合。免疫治疗策略是针对CSCs具有前景的新治疗方式。在此，我们综述了免疫治疗策略，如树突状细胞（DC）疫苗、嵌合抗原受体（CAR）工程免疫细胞、自然杀伤细胞（NK细胞）疗法、单克隆抗体（mAbs）、检查点抑制剂以及溶瘤病毒（OVs）在临床前和临床研究中对CSCs的靶向作用。本综述将主要关注血液系统恶性肿瘤，但也会描述实体癌。
