Dianat-Moghadam Hassan, Sharifi Mohammadreza, Salehi Rasoul, Keshavarz Mohsen, Shahgolzari Mehdi, Amoozgar Zohreh
Department of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran; Pediatric Inherited Diseases Research Center, Isfahan University of Medical Sciences, Isfahan, Iran.
Department of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran.
Cancer Lett. 2023 Feb 1;554:216007. doi: 10.1016/j.canlet.2022.216007. Epub 2022 Nov 14.
Intra-tumoral immune cells promote the stemness of cancer stem cells (CSCs) in the tumor microenvironment (TME). CSCs promote tumor progression, relapse, and resistance to immunotherapy. Cancer stemness induces the expression of neoantigens and neo-properties in CSCs, creating an opportunity for targeted immunotherapies. Isolation of stem-like T cells or retaining stemness in T clonotypes strategies produces exhaustion-resistance T cells with superior re-expansion capacity and long-lasting responses after adoptive cell therapies. Stem cells-derived NK cells may be the next generation of NK cell products for immunotherapy. Here, we have reviewed mechanisms by which stemness factors modulated the immunoediting of the TME and summarized the potentials of CSCs in the development of immunotherapy regimens, including CAR-T cells, CAR-NK cells, cancer vaccines, and monoclonal antibodies. We have discussed the natural or genetically engineered stem-like T cells and stem cell-derived NK cells with increased cytotoxicity to tumor cells. Finally, we have provided a perspective on approaches that may improve the therapeutic efficacy of these novel adoptive cell-based products in targeting immunosuppressive TME.
肿瘤内免疫细胞在肿瘤微环境（TME）中促进癌症干细胞（CSCs）的干性。CSCs促进肿瘤进展、复发和对免疫疗法的抗性。癌症干性诱导CSCs中新抗原和新特性的表达，为靶向免疫疗法创造了机会。分离干细胞样T细胞或在T克隆型策略中保留干性可产生具有卓越再扩增能力且在过继性细胞疗法后具有持久反应的抗耗竭T细胞。干细胞衍生的NK细胞可能是免疫疗法的下一代NK细胞产品。在此，我们综述了干性因子调节TME免疫编辑的机制，并总结了CSCs在免疫治疗方案开发中的潜力，包括嵌合抗原受体T细胞（CAR-T细胞）、嵌合抗原受体NK细胞（CAR-NK细胞）、癌症疫苗和单克隆抗体。我们讨论了对肿瘤细胞具有增强细胞毒性的天然或基因工程改造的干细胞样T细胞和干细胞衍生的NK细胞。最后，我们对可能提高这些新型过继性细胞产品在靶向免疫抑制性TME方面治疗效果的方法提出了展望。
