Agudo Judith, Miao Yuxuan
Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, MA, USA.
Department of Immunology, Harvard Medical School, Boston, MA, USA.
Nat Rev Cancer. 2025 Jan;25(1):27-40. doi: 10.1038/s41568-024-00760-0. Epub 2024 Oct 25.
Immunotherapy has become a key new pillar of cancer treatment, and this has sparked interest in understanding mechanisms of cancer immune evasion. It has long been appreciated that cancers are constituted by heterogeneous populations of tumour cells. This feature is often fuelled by specialized cells that have molecular programs resembling tissue stem cells. Although these cancer stem cells (CSCs) have capacity for unlimited self-renewal and differentiation, it is increasingly evident that some CSCs are capable of achieving remarkable immune resistance. Given that most immunotherapy regiments have overlooked CSC-specific immune-evasive mechanisms, many current treatment strategies often lead to cancer relapse. This Review focuses on advancements in understanding how CSCs in solid tumours achieve their unique immune-evasive properties, enabling them to drive tumour regrowth. Moreover, as cancers often arise from tissue stem cells that acquired oncogenic mutations, we discuss how tissue stem cells undergoing malignant transformation activate intrinsic immune-evasive mechanisms and establish close interactions with suppressive immune cells to escape immune surveillance. In addition, we summarize how in advanced disease stages, CSCs often hijack features of normal stem cells to resist antitumour immunity. Finally, we provide insights in how to design a new generation of cancer immunotherapies to ensure elimination of CSCs.
免疫疗法已成为癌症治疗的一个关键新支柱，这引发了人们对了解癌症免疫逃逸机制的兴趣。长期以来，人们一直认识到癌症是由异质性肿瘤细胞群体构成的。这一特征通常由具有类似于组织干细胞分子程序的特化细胞所推动。尽管这些癌症干细胞（CSCs）具有无限自我更新和分化的能力，但越来越明显的是，一些癌症干细胞能够实现显著的免疫抵抗。鉴于大多数免疫治疗方案都忽略了癌症干细胞特异性的免疫逃逸机制，许多当前的治疗策略往往导致癌症复发。本综述重点介绍了在理解实体瘤中的癌症干细胞如何获得其独特的免疫逃逸特性从而驱动肿瘤再生方面所取得的进展。此外，由于癌症通常起源于获得致癌突变的组织干细胞，我们讨论了发生恶性转化的组织干细胞如何激活内在的免疫逃逸机制，并与抑制性免疫细胞建立密切相互作用以逃避免疫监视。另外，我们总结了在疾病晚期，癌症干细胞如何经常利用正常干细胞的特征来抵抗抗肿瘤免疫。最后，我们就如何设计新一代癌症免疫疗法以确保消除癌症干细胞提供了见解。
