FGL2 promotes tumor progression via inducing TIGIT expression on T cells in tumor microenvironment of glioma

Abstract

Abstract Glioblastoma multiforme (GBM) is the most common primary brain tumor with a median survival of only 14.6 months. Our previous work shows that FGL2 promotes glioma tumor growth and the expression levels of FGL2 positively correlated with glioma grade in patients. T cell Ig and ITIM domain (TIGIT) is an inhibitory receptor expressed by activated T cells, Tregs, and NK cells. Here we found that there is a statistically significant positive correlation between FGL2 and TIGIT mRNA expression level in both low grade glioma database (TCGA, provisional) and glioblastoma multiforme database (TCGA, provisional). Future, FGL2 and TIGIT are coordinately expressed by human tumor-infiltrating lymphocytes of glioma as detected by flow cytometry. In addition, TIGIT expression on T cells which suppresses their function, can be induced by initial T cell activation or FGL2 in vitro. Induced TIGIT expression upon initial T cell activation is suppressed in FGL2KO T cells which has higher tumor-killing ability than WT T cells. Therefore, our results show that FGL2 induces TIGIT expression in brain-infiltrated lymphocytes which suppresses anti-tumor immune response in glioma. By this mechanism, FGL2 promotes tumor progression of glioma.