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

In this study, we found that ISG20 expression is associated with many chemokines, leading to tumor infiltration of a variety of immune cells. CCL2/CCR2 is known for recruiting monocytes to the sites of inflammation produced by either tissue injury or infection, and augments the accumulation of regulatory Foxp3(+)CD4(+) T cells and of nitric oxide-and YM-1-expressing macrophages and microglia. 52 CCL5 induces chemotaxis in T cells and monocytes. 53-56 CCL23 might play vital roles in inflammation through the recruitment of macrophages and dendritic cells. 57 CCRL2/CXCR2 is the main neutrophil attractor in vitro, 58 and is involved in the control of both innate and adaptive immune responses. 59 CXCR6, a chemokine receptor for CXCL16 that is expressed on a subset of CD4 + T helper 1 cells and natural killer T cells, is involved in lymphocyte homing and modulates the development and progression of atherosclerosis. 60 Collectively, elevated expression of these chemokines may contribute to glioma progression by recruiting macrophages and neutrophils to the local tumor environment. Nevertheless, we did not find a significant association of microglia with ISG20 expression, suggesting that the ISG20-associated macrophages were monocyte-derived instead of residual microglial cells. 61 Moreover, we found that the majority of adaptive immune cells subtypes, such as Tgd, Tcm, Tfh, and Tem were less abundant, with increased expression of ISG20, which suggested that high ISG20 expression is associated with inefficient antitumor immunity. However, we did not find any correlation between ISG20 and natural killer cells, CD4 + T cells, and CD8 + T cells. We also detected a positive correlation of ISG20 levels with PD-1/PD-L1 and CTLA4 expression, further inhibiting T cell function and leading to tumor evasion of immune responses. 62 The association of ISG20 expression with patient survival did not reach statistical significance for WHO grade II tumors and in the IDHmut tumors in TCGA cohort, although we found the same trend as the other groups. This may be due to the relatively longer survival of these patients. Further studies with more extended follow-up are needed to determine the prognostic value of ISG20 in these subgroups of patients.