ADGRL4/ELTD1 Expression in Breast Cancer Cells Induces Vascular Normalization and Immune Suppression

Area of Science:

• Oncology
• Immunology
• Vascular Biology

Background:

• ELTD1/ADGRL4 is upregulated in various tumor vasculature, often linked to prognosis.
• ELTD1 expression in tumor cells shows varied prognostic value across cancer types like HCC and glioblastoma.

Purpose of the Study:

• To investigate the role of ELTD1 in breast tumor growth, metastasis, and immune microenvironment.
• To explore the therapeutic implications of ELTD1 expression in breast cancer.

Main Methods:

• Analysis of ELTD1 expression in human breast tumors.
• Utilized immunocompetent syngeneic mouse breast cancer models to study Eltd1-expressing tumors.
• Assessed tumor vascularization, immune cell infiltration, and response to therapy.

Main Results:

• 35% of human breast tumors showed ELTD1 positivity, with 9% high expression correlating with improved relapse-free survival.
• Eltd1-expressing mouse tumors exhibited faster growth, increased metastasis, larger/better perfused vessels, and enhanced systemic immune effects.
• An immunosuppressive microenvironment was observed, with increased M2-like macrophages and PD-L1 expression, despite an NY-ESO-1 immune response.
• Eltd1-positive tumors showed better response to chemotherapy.

Conclusions:

• ELTD1 expression in breast tumors promotes an immunosuppressive microenvironment and enhances vascularization.
• ELTD1 may improve therapeutic antibody delivery, potentially reversing immunosuppression and enhancing responses to chemotherapy and radiotherapy.
• ELTD1 could serve as a predictive biomarker for specific immunotherapies and chemo/radiotherapies in a subset of breast tumors.