Woo Seng-Ryong, Corrales Leticia, Gajewski Thomas F
Department of Pathology, The University of Chicago, Chicago, IL, USA.
Department of Pathology, The University of Chicago, Chicago, IL, USA; Department of Medicine, Section of Hematology/Oncology, The University of Chicago, Chicago, IL, USA.
Trends Immunol. 2015 Apr;36(4):250-6. doi: 10.1016/j.it.2015.02.003. Epub 2015 Mar 7.
A major subset of patients with advanced solid tumors show a spontaneous T cell-inflamed tumor microenvironment, which has prognostic import and is associated with clinical response to immunotherapies. As such, understanding the mechanisms governing the generation of spontaneous T cell responses in only a subset of patients is critical for advancing immunotherapeutic approaches further. Here, we discuss the characteristics of T cell-inflamed versus non-inflamed tumors, including a type I interferon (IFN) signature associated with T cell priming against tumor antigens. We review recent findings that have pointed towards the STING (stimulator of interferon genes) pathway of cytosolic DNA sensing as an important innate immune sensing mechanism driving type I IFN production in the tumor context. Knowledge of this pathway is guiding the further development of novel immunotherapeutic strategies.
晚期实体瘤患者中的一个主要亚群表现出一种自发的T细胞炎症性肿瘤微环境,这具有预后意义,并与免疫治疗的临床反应相关。因此,了解仅在一部分患者中控制自发T细胞反应产生的机制对于进一步推进免疫治疗方法至关重要。在这里,我们讨论了T细胞炎症性肿瘤与非炎症性肿瘤的特征,包括与针对肿瘤抗原的T细胞启动相关的I型干扰素(IFN)特征。我们回顾了最近的研究发现,这些发现指出胞质DNA感应的STING(干扰素基因刺激物)途径是在肿瘤环境中驱动I型干扰素产生的重要先天性免疫感应机制。对该途径的了解正在指导新型免疫治疗策略的进一步发展。