Research Paper Volume 12, Issue 2 pp 1656—1684
Elevated lymphocyte specific protein 1 expression is involved in the regulation of leukocyte migration and immunosuppressive microenvironment in glioblastoma
- 1 Department of Neurosurgery, The First Hospital of China Medical University, Shenyang, Liaoning 110001, China
- 2 Department of Biochemistry, School of Life Science, China Medical University, Shenyang, Liaoning 110122, China
- 3 College of Applied Technology, China Medical University, Shenyang, Liaoning 110122, China
Received: June 12, 2019 Accepted: January 2, 2020 Published: January 29, 2020
https://doi.org/10.18632/aging.102706How to Cite
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.