Oh Se Jin, Lee Jaeyoon, Kim Yukang, Song Kwon-Ho, Cho Eunho, Kim Minsung, Jung Heejae, Kim Tae Woo
Department of Biochemistry & Molecular Biology, Korea University College of Medicine, Seoul 02841, Korea.
Department of Biomedical Science, Korea University College of Medicine, Seoul 02841, Korea.
Immune Netw. 2020 Jan 20;20(1):e7. doi: 10.4110/in.2020.20.e7. eCollection 2020 Feb.
Cancer immunotherapy, in the form of vaccination, adoptive cellular transfer, or immune checkpoint inhibitors, has emerged as a promising practice within the field of oncology. However, despite the developing field's potential to revolutionize cancer treatment, the presence of immunotherapeutic-resistant tumor cells in many patients present a challenge and limitation to these immunotherapies. These cells not only indicate immunotherapeutic resistance, but also show multi-modal resistance to conventional therapies, abnormal metabolism, stemness, and metastasis. How can immunotherapeutic-resistant tumor cells render multi-malignant phenotypes? We reasoned that the immune-refractory phenotype could be associated with multi-malignant phenotypes and that these phenotypes are linked together by a factor that acts as the master regulator. In this review, we discussed the role of the embryonic transcription factor NANOG as a crucial master regulator we named "common factor" in multi-malignant phenotypes and presented strategies to overcome multi-malignancy in immunotherapeutic-resistant cancer by restraining the NANOG-mediated multi-malignant signaling axis. Strategies that blunt the NANOG axis could improve the clinical management of therapy-refractory cancer.
癌症免疫疗法，包括疫苗接种、过继性细胞转移或免疫检查点抑制剂，已成为肿瘤学领域一种有前景的治疗方法。然而，尽管该新兴领域有潜力彻底改变癌症治疗方式，但许多患者体内存在对免疫疗法耐药的肿瘤细胞，这对这些免疫疗法构成了挑战和限制。这些细胞不仅表现出对免疫疗法的耐药性，还对传统疗法具有多模式耐药性、异常代谢、干性和转移能力。对免疫疗法耐药的肿瘤细胞如何呈现多种恶性表型？我们推测免疫难治性表型可能与多种恶性表型相关，并且这些表型由一种作为主要调节因子的因素联系在一起。在本综述中，我们讨论了胚胎转录因子NANOG作为一种关键的主要调节因子（我们称之为“共同因子”）在多种恶性表型中的作用，并提出了通过抑制NANOG介导的多种恶性信号轴来克服免疫疗法耐药癌症中的多种恶性状态的策略。削弱NANOG轴的策略可能会改善难治性癌症的临床管理。
