Roerden Malte, Spranger Stefani
Koch Institute for Integrative Cancer Research, Massachusetts Institute for Technology, Cambridge, MA, USA.
Department of Biology, Massachusetts Institute for Technology, Cambridge, MA, USA.
Nat Rev Immunol. 2025 May;25(5):353-369. doi: 10.1038/s41577-024-01111-8. Epub 2025 Jan 2.
Cancers can avoid immune-mediated elimination by acquiring traits that disrupt antitumour immunity. These mechanisms of immune evasion are selected and reinforced during tumour evolution under immune pressure. Some immunogenic subclones are effectively eliminated by antitumour T cell responses (a process known as immunoediting), which results in a clonally selected tumour. Other cancer cells arise to resist immunoediting, which leads to a tumour that includes several distinct cancer cell populations (referred to as intratumour heterogeneity (ITH)). Tumours with high ITH are associated with poor patient outcomes and a lack of responsiveness to immune checkpoint blockade therapy. In this Review, we discuss the different ways that cancer cells evade the immune system and how these mechanisms impact immunoediting and tumour evolution. We also describe how subclonal antigen presentation in tumours with high ITH can result in immune evasion.
癌症可通过获得破坏抗肿瘤免疫的特性来逃避免疫介导的清除。这些免疫逃逸机制在免疫压力下的肿瘤进化过程中被选择并强化。一些免疫原性子克隆会被抗肿瘤T细胞反应有效清除（这一过程称为免疫编辑），从而产生克隆选择的肿瘤。其他癌细胞则产生以抵抗免疫编辑，导致肿瘤包含几个不同的癌细胞群体（称为肿瘤内异质性（ITH））。ITH高的肿瘤与患者预后不良以及对免疫检查点阻断疗法缺乏反应相关。在本综述中，我们讨论癌细胞逃避免疫系统的不同方式，以及这些机制如何影响免疫编辑和肿瘤进化。我们还描述了ITH高的肿瘤中的亚克隆抗原呈递如何导致免疫逃逸。
