文章：

实体恶性肿瘤的干性：应对免疫攻击

Stemness in solid malignancies: coping with immune attack

原文发布日期：2024-10-25

DOI: 10.1038/s41568-024-00760-0

类型: Review Article

开放获取: 否

英文摘要：

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.

摘要翻译： 

免疫疗法已成为癌症治疗的关键新支柱，这激发了人们对理解癌症免疫逃逸机制的兴趣。长期以来，人们认识到癌症由异质性的肿瘤细胞群构成。这一特征通常受到具有类似组织干细胞分子程序的特殊细胞驱动。尽管这些癌症干细胞具有无限自我更新和分化的能力，但越来越明显的是，部分癌症干细胞能够实现显著的免疫抵抗。鉴于大多数免疫疗法方案忽视了癌症干细胞特异性免疫逃逸机制，当前许多治疗策略常导致癌症复发。本综述重点关注在理解实体瘤中癌症干细胞如何获得独特免疫逃逸特性方面的研究进展，这些特性使其能够驱动肿瘤再生。此外，由于癌症常源于获得致癌突变的组织干细胞，我们讨论了经历恶性转化的组织干细胞如何激活内在免疫逃逸机制，并与抑制性免疫细胞建立紧密互动以逃避免疫监视。同时，我们总结了在疾病晚期阶段，癌症干细胞如何劫持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。

原文链接：

Stemness in solid malignancies: coping with immune attack