Pan Qin, Li Qiao, Liu Shuang, Ning Ning, Zhang Xiaolian, Xu Yingxin, Chang Alfred E, Wicha Max S
University of Michigan Comprehensive Cancer Center, Ann Arbor, Michigan, USA.
State Key Laboratory of Virology, Department of Immunology, Hubei Province Key Laboratory of Allergy and Immunology, Wuhan University School of Medicine, Wuhan, Hubei Province, People's Republic of China.
Stem Cells. 2015 Jul;33(7):2085-92. doi: 10.1002/stem.2039. Epub 2015 May 13.
Cancer stem cells (CSCs) represent a small subset of tumor cells which have the ability to self-renew and generate the diverse cells that comprise the tumor bulk. They are responsible for local tumor recurrence and distant metastasis. However, they are resistant to conventional radiotherapy and chemotherapy. Novel immunotherapeutic strategies that specifically target CSCs may improve the efficacy of cancer therapy. To immunologically target CSC phenotypes, innate immune responses to CSCs have been reported using Natural killer cells and γδ T cells. To target CSC specifically, in vitro CSC-primed T cells have been successfully generated and shown targeting of CSCs in vivo after adoptive transfer. Recently, CSC-based dendritic cell vaccine has demonstrated significant induction of anti-CSC immunity both in vivo in immunocompetent hosts and in vitro as evident by CSC reactivity of CSC vaccine-primed antibodies and T cells. In addition, identification of specific antigens or genetic alterations in CSCs may provide more specific targets for immunotherapy. ALDH, CD44, CD133, and HER2 have served as markers to isolate CSCs from a number of tumor types in animal models and human tumors. They might serve as useful targets for CSC immunotherapy. Finally, since CSCs are regulated by interactions with the CSC niche, these interactions may serve as additional targets for CSC immunotherapy. Targeting the tumor microenvironment, such as interrupting the immune cell, for example, myeloid-derived suppressor cells, and cytokines, for example, IL-6 and IL-8, as well as the immune checkpoint (PD1/PDL1, etc.) may provide additional novel strategies to enhance the immunological targeting of CSCs.
癌症干细胞（CSCs）是肿瘤细胞中的一小部分，具有自我更新能力，并能产生构成肿瘤主体的各种细胞。它们导致局部肿瘤复发和远处转移。然而，它们对传统放疗和化疗具有抗性。专门针对癌症干细胞的新型免疫治疗策略可能会提高癌症治疗的疗效。为了从免疫学上靶向癌症干细胞表型，已报道利用自然杀伤细胞和γδT细胞对癌症干细胞产生先天性免疫反应。为了特异性靶向癌症干细胞，体外已成功产生经癌症干细胞致敏的T细胞，并在过继转移后显示出在体内对癌症干细胞的靶向作用。最近，基于癌症干细胞的树突状细胞疫苗已证明，在免疫活性宿主体内以及体外均能显著诱导抗癌症干细胞免疫，这从癌症干细胞疫苗致敏的抗体和T细胞对癌症干细胞的反应性中可以明显看出。此外，识别癌症干细胞中的特定抗原或基因改变可能为免疫治疗提供更具体的靶点。乙醛脱氢酶（ALDH）、CD44、CD133和人表皮生长因子受体2（HER2）已作为从动物模型和人类肿瘤的多种肿瘤类型中分离癌症干细胞的标志物。它们可能是癌症干细胞免疫治疗的有用靶点。最后，由于癌症干细胞受与癌症干细胞生态位相互作用的调节，这些相互作用可能成为癌症干细胞免疫治疗的额外靶点。靶向肿瘤微环境，例如阻断免疫细胞（如髓源性抑制细胞）和细胞因子（如白细胞介素-6和白细胞介素-8），以及免疫检查点（程序性死亡蛋白1/程序性死亡蛋白配体1等），可能提供额外的新策略来增强对癌症干细胞的免疫靶向作用。
