Translational Cancer Genomics, Wellcome Sanger Institute, Hinxton, UK.
Open Targets, Cambridge, UK.
Cell Commun Signal. 2023 Mar 2;21(1):45. doi: 10.1186/s12964-023-01063-x.
Oncogenic driver mutations have implications that extend beyond cancer cells themselves. Aberrant tumour cell signalling has various effects on the tumour microenvironment and anti-tumour immunity, with important consequences for therapy response and resistance. We provide an overview of how mutant RAS, one of the most prevalent oncogenic drivers in cancer, can instigate immune evasion programs at the tumour cell level and through remodelling interactions with the innate and adaptive immune cell compartments. Finally, we describe how immune evasion networks focused on RAS, and the immune checkpoint molecule PD-L1 can be disrupted through therapeutic intervention, and discuss potential strategies for combinatorial treatment. Video abstract.
致癌驱动突变的影响不仅局限于癌细胞本身。异常的肿瘤细胞信号转导对肿瘤微环境和抗肿瘤免疫有各种影响,对治疗反应和耐药性有重要影响。我们概述了最常见的致癌驱动因子之一突变 RAS 如何在肿瘤细胞水平以及通过重塑与先天和适应性免疫细胞区室的相互作用引发免疫逃逸程序。最后,我们描述了如何通过治疗干预来破坏针对 RAS 的免疫逃逸网络和免疫检查点分子 PD-L1,并讨论了联合治疗的潜在策略。视频摘要。