文章：

癌症免疫学和免疫治疗中的交叉启动

Cross-priming in cancer immunology and immunotherapy

原文发布日期：2025-01-29

DOI: 10.1038/s41568-024-00785-5

类型: Review Article

开放获取: 否

英文摘要：

Cytotoxic T cell immune responses against cancer crucially depend on the ability of a subtype of professional antigen-presenting cells termed conventional type 1 dendritic cells (cDC1s) to cross-present antigens. Cross-presentation comprises redirection of exogenous antigens taken from other cells to the major histocompatibility complex class I antigen-presenting machinery. In addition, once activated and having sensed viral moieties or T helper cell cooperation via CD40–CD40L interactions, cDC1s provide key co-stimulatory ligands and cytokines to mount and sustain CD8+ T cell immune responses. This regulated process of cognate T cell activation is termed cross-priming. In cancer mouse models, CD8+ T cell cross-priming by cDC1s is crucial for the efficacy of most, if not all, immunotherapy strategies. In patients with cancer, the presence and abundance of cDC1s in the tumour microenvironment is markedly associated with the level of T cell infiltration and responsiveness to immune checkpoint inhibitors. Therapeutic strategies to increase the numbers of cDC1s using FMS-like tyrosine kinase 3 ligand (FLT3L) and/or their activation status show evidence of efficacy in cancer mouse models and are currently being tested in initial clinical trials with promising results so far.

摘要翻译： 

细胞毒性T细胞针对癌症的免疫应答关键依赖于一种称为经典1型树突状细胞（cDC1s）的专业抗原呈递细胞亚型交叉呈递抗原的能力。交叉呈递是指将取自其他细胞的外源性抗原引导至主要组织相容性复合体I类抗原呈递机制的过程。此外，一旦被激活并通过感知病毒组分或T辅助细胞经由CD40-CD40L相互作用提供的协同信号，cDC1s可提供关键共刺激配体和细胞因子以激发并维持CD8+T细胞免疫应答。这种受调控的同源T细胞激活过程被称为交叉启动。在癌症小鼠模型中，cDC1s介导的CD8+T细胞交叉启动对大多数（若非全部）免疫治疗策略的功效至关重要。在癌症患者中，肿瘤微环境中cDC1s的存在及丰度与T细胞浸润水平及对免疫检查点抑制剂的应答反应显著相关。通过使用FMS样酪氨酸激酶3配体（FLT3L）增加cDC1s数量及/或增强其活化状态的治疗策略，已在癌症小鼠模型中显示疗效，目前正在初期临床试验中进行验证，迄今已取得令人鼓舞的结果。

原文链接：

Cross-priming in cancer immunology and immunotherapy