Elevated lymphocyte specific protein 1 expression is involved in the regulation of leukocyte migration and immunosuppressive microenvironment in glioblastoma

Abstract

Immune cell infiltration mediates therapeutic response to immune therapies. The investigation on the genes regulating leukocyte migration may help us to understand the mechanisms regulating immune cell infiltration in tumor microenvironment. Here, we collected the data from Chinese Glioma Genome Atlas (CGGA) and The Cancer Genome Atlas (TCGA) to analyze the expression of leukocyte migration related genes in glioblastoma (GBM). Lymphocyte specific protein 1 (LSP1) was identified as the only gene in this family which not only has an elevated expression, but also serve as an independent predictive factor for progressive malignancy in glioma. We further confirmed these results in clinical glioma samples by quantitative PCR, immunofluorescence, immunohistochemistry, and western blot. Moreover, LSP1 expression was closely related to the response to radio-and chemotherapy in GBM, and positively correlated with immunosuppressive cell populations, including M2 macrophages, neutrophil, and regulatory T cell. Additionally, elevated LSP-1 expression enhanced the expression of immunosuppression related genes like programmed cell death 1 (PD1) and leukocyte associated immunoglobulin like receptor 1 (LAIR1) in macrophages. LSP1 also promoted the migration of macrophages. Together, our study suggests a novel role of LSP1 contributing to immunosuppressive microenvironment in GBM and serving as a potential therapeutic target for it.

Identification of Tumor Microenvironment-Related Prognostic Biomarkers in Luminal Breast Cancer

“…Of the 593 shared DEmRNAs, 577 were upregulated, accounting for 97.3%; thus, we mainly focused on their biological functions. The results indicated that many of them were associated with TME-related processes, such as the immune response, leukocyte migration, antigen binding, and the CAM pathway ( Harjunpaa et al, 2019 ; Cao et al, 2020 ; Messex et al, 2020 ; Sulea et al, 2020 ). Next, ceRNA and PPI networks were constructed.…”

In silico identification of the prognostic biomarkers and therapeutic targets associated with cancer stem cell characteristics of glioma

“…According to the pathway analysis, we found the highly enrichment of leukocyte migration and neuroactive ligand–receptor interaction. The leukocyte migration often regulates immunosuppressive microenvironment and the lymphocyte specific protein 1 (LSP1)-induced immunosuppressive microenvironment has been reported to contribute to GBM [ 26 ]. In addition, CD133 + and Nestin + glioma stem-like cells could also regulate SDF-1α and CXCR4, which subsequently promote leukocyte migration and glioma progression [ 27 ].…”

Immunological and clinicopathological characteristics of C1RL in 2120 glioma patients

“…M2 macrophages promotes glioma growth [27]. The ESTIMATE algorithm is a well-accepted method to predict the tumour purity in genomic and transcriptomic studies [36,37]. Besides, CIBERSORT algorithm, also known as in silico flow cytometry, was developed to accurately assess the infiltration of many leukocyte subsets in bulk tumour samples, along with a signature genes file that enumerates the genes that define the signature expression profile for each immune cell [38].…”