ISG20 promotes local tumor immunity and contributes to poor survival in human glioma

Gao, Mengqi; Lin, Yi; Liu, Xing; Li, Yiming; Zhang, Chuanbao; Wang, Zheng; Wang, Zhiliang; Wang, Yulin; Guo, Zongze

Mounting evidence suggests that glioma with an IDH mutation has suppressed immunity. 16 Inflammation may promote the proliferation and survival of malignant cells and metastasis, contribute to overturning adaptive immunity, and change tumor responses to chemotherapeutic agents. 19 A large proportion of the glioma tumor microenvironment consists of an inflammatory infiltrate predominated by macrophages, which are thought to be subverted by glioblastoma cells for tumor growth. 20, 21 In gliomas, IDHwt tumors are associated with infiltration of more immune-related components, contributing to poor survival. However, the associated molecular mechanisms remain poorly understood, and thus more extensive research in this area could provide insight toward improved diagnosis and treatment. [22] [23] [24] [25] Toward this end, we have identified that ISG20 may play a key role in mediating the IDH-related immune response in the glioma microenvironment. The ISG20 gene, located at chromosome 15q26.1, encodes a 20-kDa protein. It was first introduced in 1997 by Celine Gongora and colleagues as an IFN-induced promyelocytic leukemia nuclear body (PML-NB)-associated protein. 26 PML-NB is reported to be extensively involved in oncogenesis and gene transcription, [27] [28] [29] and the function differs according to its binding protein. [30] [31] [32] [33] The endogenous ISG20 protein is present both in the nucleolus and in the Cajal bodies, and participates in the maturation of small nucleolar RNAs and ribosomal RNAs, and in ribosome biogenesis, [34] [35] [36] [37] [38] [39] leading to the control of RNA stability. 40,41 ISG20 can be induced by type I and type II IFNs, 42,43 and its expression has been shown to be elevated during infection [44] [45] [46] and in several types of cancers. 33, [47] [48] [49] [50] [51] However, the exact function and mechanism of action of this protein remain elusive.