Molecular and clinical characterization of Galectin‐9 in glioma through 1,027 samples

Abstract

In recent years, research on glioma immunotherapy have grown rapidly. However, the autoimmune-like side effects that are caused by blocking immunological checkpoints hinder their clinical application in gliomas currently. Galectin-9, a ligand for T-cell immunoglobulin mucin 3, has shed a new light on the treatment of malignant glioma.However, the potential mechanism of Galectin-9 is still under discussion. In this study, first, we methodically gathered 1,027 glioma patients with RNA-seq and 986 patients with survival data to explore the role and mechanism of Galectin-9 in gliomas.Second, we analyzed glioma samples from 50 patients in the Department of Neurosurgery, Tianjin Medical University General Hospital. Finally, we found that Galectin-9 was strongly upregulated in glioblastoma multiforme compared with normal brain tissues and lower-grade glioma. Patients with Galectin-9 overexpression had a significantly shorter overall survival. Moreover, the tissue microarray data displayed that the expression of Galectin-9 in the core of tumor is higher than that in the border and was correlated with the shorter survival in glioma patients. Galectin-9 is more highly expressed in the mesenchymal subtype of glioblastoma multiforme than in the other subtypes. Simultaneously, Galectin-9 was closely associated with the immune response and lymphocyte activation, especially T-cell activation. To further determine the underlying role of Galectin-9 in the immune response, we selected seven immune metagenes. Through cluster analysis and correlation analysis, we discovered that Galectin-9 was highly correlated with immune checkpoint molecules and M2 tumor-associated macrophages. In summary, Galectin-9 serves as a potential therapeutic target to treat glioblastoma multiforme. K E Y W O R D S checkpoint inhibitors, Galectin-9, glioblastoma multiforme, immune response, tumor-associated macrophages ---

The immune landscape of primary central nervous system diffuse large B cell lymphoma

“…High LGALS9/HAVCR2 co-expression scores (the so-called L-R scores) were found in every immune subtype of PCNSL, although they were higher in the immune-rich tumors. Concomitant upregulation of TIM-3 and galectin-9 proteins occurred in PCNSL tumors compared to normal brain tissue, an observation already reported for other tumors in the brain [47][48][49]. In contrast to PD-1, we show that TIM-3 was mostly produced by both tumor cells and TAMs in PCNSL, an observation already reported for DLBCL [50], whereas it is mainly produced by CD8+ T cells and microglial cells in brain tumors, such as glioma [47].…”

Immunological and clinicopathological characteristics of C1RL in 2120 glioma patients

“…LGALS9 [21], and TGFB1 [22] play immunosuppressive roles in glioma. Our results showed that C1RL expression exhibited positive relations with CD86, LGALS9, and TGFB1 (Fig 3.A-L).…”

“…But we still unsure whether C1RL promotes anti-tumour immune response or suppress it. Given that CD86 [20], LGALS9 [21], and TGFB1 [22] play immunosuppressive roles in glioma, we further investigated the expressing relationship between C1RL and these immunosuppressive genes. Besides, low tumour purity [26] and high M2 macrophages in ltration [27] were reported to promotes glioma progression.…”

Immunological and clinicopathological characteristics of C1RL in 2120 glioma patients

“…TGFB1 encodes a secreted ligand in the transforming growth factor-beta (TGF-beta) superfamily of proteins. CD86 [20], LGALS9 [21], and TGFB1 [22] play immunosuppressive roles in glioma. Our results showed that C1RL expression exhibited positive relations with CD86, LGALS9, and TGFB1 (Fig.…”