LPL-Positive Endothelial Cells Control T-cell Homing in Liver Metastasis

Area of Science:

• Immunology
• Oncology
• Vascular Biology

Background:

• Combination therapies targeting tumor vasculature show potential against immunotherapy resistance.
• The mechanisms by which vascular modulation enhances antitumor T-cell responses are not fully understood.

Purpose of the Study:

• To investigate the role of tumor endothelial cells (TECs) in modulating T-cell responses within liver metastases.
• To identify specific molecular pathways in TECs that promote effective antitumor immunity.

Main Methods:

• Transcriptional profiling of liver metastasis-associated peritumoral and tumor endothelial cells (TECs) following T-cell intervention.
• Analysis of lipoprotein lipase (LPL) expression in TECs and its functional impact on T-cell trafficking and antigen presentation.
• Correlation analysis of LPL+ blood vessels and T-cell accumulation in human liver metastasis samples.

Main Results:

• A subpopulation of TECs expressing high levels of lipoprotein lipase (LPL+ TECs) was identified.
• LPL+ TECs were found to facilitate the homing of activated CD8+ T cells into the tumor microenvironment.
• LPL enhances MHC-I-dependent cross-presentation of tumor antigens on TECs, improving T-cell recognition and trafficking.
• A positive correlation was observed between intratumoral LPL+ blood vessels and T-cell infiltration in human liver metastases.

Conclusions:

• TECs play a crucial role in orchestrating effective T-cell responses by overcoming insufficient tumor antigen presentation.
• LPL+ TECs are key regulators of CD8+ T-cell homing into immunologically "cold" tumors.
• Targeting LPL+ TECs to enhance MHC-I cross-presentation offers a promising strategy to boost antitumor immunotherapy.