GPR65 contributes to constructing immunosuppressive microenvironment in glioma.

Area of Science:

• Oncology
• Immunology
• Genetics

Background:

• Glioma, particularly glioblastoma, features a heterogeneous and immunosuppressive tumor microenvironment, contributing to poor treatment outcomes.
• M2 macrophages are abundant in glioma tissue, potentially influencing tumor progression and immune evasion.

Purpose of the Study:

• To identify key genes associated with M2 macrophages in glioma.
• To investigate the role of GPR65 in glioma's tumor microenvironment and its potential as a therapeutic target.

Main Methods:

• Weighted Gene Co-expression Network Analysis (WGCNA) to identify gene modules.
• Expression and prognosis analysis to correlate gene expression with glioma malignancy.
• Single-cell data analysis and immunofluorescence to validate protein expression and localization.
• Functional experiments to assess the impact of GPR65 inhibition on macrophage polarization.

Main Results:

• GPR65 was identified as a hub gene in the M2 macrophage-related module in glioma.
• GPR65 expression positively correlated with glioma malignancy and poor prognosis.
• GPR65 was highly expressed in macrophages within the glioma microenvironment, particularly in vascular proliferation areas.
• Inhibition of GPR65 reduced M2 macrophage polarization and disrupted the pro-tumorigenic interaction between macrophages and glioma cells.

Conclusions:

• GPR65 plays a significant role in the malignant behavior of the glioma microenvironment.
• GPR65 represents a potential therapeutic target for modulating the glioma immune microenvironment and improving treatment efficacy.