文章：

致癌途径对逃避抗肿瘤免疫反应的影响

Impact of oncogenic pathways on evasion of antitumour immune responses

原文发布日期：2018-01-12

DOI: 10.1038/nrc.2017.117

类型: Review Article

开放获取: 否

要点：

1. T cell infiltration into the tumour microenvironment (TME) is an important feature for the therapeutic activity of checkpoint blockade therapy.
2. While T cell activation can be influenced in multiple ways, oncogenic signalling within tumour cells has the potential to mediate T cell exclusion from the tumour microenvironment.
3. Some oncogenic pathways, such as activation of WNT–β-catenin and MYC, mediate failed T cell recruitment through failed accumulation or activation of antigen-presenting cells.
4. Within the antigen-presenting cell compartment, dendritic cells driven by the transcription factor basic leucine zipper transcriptional factor ATF-like 3 (BATF3) seem to be of critical importance for priming of tumour-specific CD8⁺ T cells.
5. Other oncogenic signalling pathways, such as loss of function of liver kinase B1 (LKB1) mutations, mediate recruitment of immune suppressive cell populations, which in turn mediate exclusion of T cells from the TME.

要点翻译：

1. T细胞向肿瘤微环境的浸润是检查点阻断疗法治疗活性的一个重要特征。
2. 尽管T细胞活化可受多种方式影响，但肿瘤细胞内的致癌信号具有介导T细胞排斥出肿瘤微环境的潜力。
3. 部分致癌通路（如WNT–β-catenin和MYC的激活）通过阻碍抗原呈递细胞的聚集或活化，导致T细胞招募失败。
4. 在抗原呈递细胞群体中，由转录因子BATF3驱动的树突状细胞对肿瘤特异性CD8+ T细胞的启动具有关键作用。
5. 其他致癌信号通路（如LKB1功能缺失突变）则会介导免疫抑制性细胞群的招募，进而导致T细胞被排斥出肿瘤微环境。

英文摘要：

Immunotherapeutic interventions are showing effectiveness across a wide range of cancer types, but only a subset of patients shows clinical response to therapy. Responsiveness to checkpoint blockade immunotherapy is favoured by the presence of a local, CD8+ T cell-based immune response within the tumour microenvironment. As molecular analyses of tumours containing or lacking a productive CD8+ T cell infiltrate are being pursued, increasing evidence is indicating that activation of oncogenic pathways in tumour cells can impair induction or execution of a local antitumour immune response. This Review summarizes our current knowledge of the influence of oncogenic effects on evasion of antitumour immunity.

摘要翻译： 

免疫治疗干预在多种癌症类型中显示出有效性，但只有部分患者对治疗产生临床反应。检查点阻断免疫治疗的反应性依赖于肿瘤微环境中存在局部的CD8+ T细胞免疫应答。随着对含有或缺乏有效CD8+ T细胞浸润的肿瘤进行分子分析，越来越多的证据表明，肿瘤细胞中致癌通路的激活会削弱局部抗肿瘤免疫应答的诱导或执行。本综述总结了我们对致癌效应影响抗肿瘤免疫逃逸的现有认识。

原文链接：

Impact of oncogenic pathways on evasion of antitumour immune responses