PDPN contributes to constructing immunosuppressive microenvironment in IDH wildtype glioma

Area of Science:

• Oncology
• Immunology
• Molecular Biology

Background:

• The tumor immunosuppressive microenvironment (IME) critically influences glioma progression and patient outcomes.
• Molecular mechanisms driving IME in glioma, particularly in IDH wildtype subtypes, require further elucidation.

Purpose of the Study:

• To investigate the prognostic value of PDPN in glioma.
• To explore the role of PDPN in shaping the tumor immunosuppressive microenvironment (IME) in glioma.

Main Methods:

• Weighted gene co-expression network analysis (WGCNA) to identify gene associations.
• Correlation analyses to assess relationships between PDPN, immune cells, and clinical parameters.
• In vitro experiments to validate cellular mechanisms.
• Least absolute shrinkage and selection operator (LASSO) regression for prognostic model development.

Main Results:

• PDPN expression is significantly associated with IDH wildtype status and higher immune scores in glioma.
• PDPN positively correlates with immune checkpoint expression, response to checkpoint blockade, tumor-associated neutrophils (TANs), and tumor-associated macrophages (TAMs).
• A prognostic model based on TANs and TAMs markers, incorporating PDPN, predicted worse outcomes.

Conclusions:

• PDPN overexpression serves as an independent prognostic indicator in IDH wildtype gliomas.
• PDPN promotes M2 macrophage polarization and neutrophil degranulation, contributing to an immunosuppressive IME.
• Targeting PDPN offers a potential strategy for combination therapy with immunotherapy in malignant gliomas.