LRG1 destabilizes tumor vessels and restricts immunotherapeutic potency

Area of Science:

• Oncology
• Vascular Biology
• Immunotherapy

Background:

• Poorly functioning tumor vasculature promotes cancer growth and hinders therapeutic delivery.
• Leucine-rich α-2-glycoprotein 1 (LRG1) is implicated in pathogenic neovascularization.
• Investigating LRG1's role in tumor vasculopathy and its therapeutic potential is crucial.

Purpose of the Study:

• To determine if LRG1 contributes to tumor vasculopathy.
• To evaluate the therapeutic utility of inhibiting LRG1 in cancer models.
• To assess the impact of LRG1 inhibition on tumor vascular function and treatment efficacy.

Main Methods:

• Analysis of tumor growth and vascular structure in wild-type and Lrg1 knockout mouse models.
• Utilizing LRG1 function-blocking antibodies as monotherapy and in combination with other treatments.
• Investigating effects on vascular function, tumor growth, and immune cell infiltration.

Main Results:

• LRG1 expression is increased in tumor endothelial cells in mouse models and human cancers.
• LRG1 inhibition (gene deletion or antibody blockade) suppressed tumor growth and improved survival.
• LRG1 blockade enhanced chemotherapy, adoptive T cell therapy, and anti-PD1 immunotherapy efficacy by improving vascular function and promoting immune cell infiltration.

Conclusions:

• LRG1 drives tumor vascular abnormalization.
• Inhibiting LRG1 is a novel strategy to improve cancer therapeutic efficacy.
• Targeting LRG1 can overcome treatment resistance and enhance anti-tumor immunity.