Shear Stress and Microbubble-Mediated Modulation of Endothelial Cell Immunobiology

Area of Science:

• Immunology
• Biotechnology
• Biomedical Engineering

Background:

• Solid tumors present an immunosuppressive microenvironment, hindering cellular immunotherapy efficacy.
• Suppressed endothelial cell adhesion molecules (CAMs) contribute to this immunosuppression.
• Microbubble-mediated focused ultrasound is a potential immunotherapy strategy that induces shear stress.

Purpose of the Study:

• To investigate the influence of fluid shear stress and microbubble-mediated ultrasound on endothelial cell immunobiology.
• To examine the modulation of CAM expression and cytokine secretion in human endothelial cells.

Main Methods:

• Utilized acoustically coupled microscopy to study human umbilical vein endothelial cells (HUVEC) and human brain endothelial cells (HBEC-5i).
• Assessed cell adhesion molecule (CAM) expression and secretion of over 90 cytokines under fluid flow and ultrasound conditions.
• Analyzed time-dependent changes in CAM expression and cytokine profiles.

Main Results:

• Fluid flow significantly modulated CAM expression, with ICAM-1 peaking at 4h in HUVEC and 24h in HBEC-5i.
• Both cell types showed enhanced chemokine secretion (e.g., IL-8, MCP-1) and differential expression of others (e.g., CCL5).
• Ultrasound exposure increased ICAM-1 expression and induced significant differential expression of 20 immune-activating cytokines.

Conclusions:

• Microbubble-mediated ultrasound regulates ICAM-1 expression and the endothelial secretome towards immune cell recruitment.
• This mechanism holds promise for reinforcing cellular immunotherapy strategies in solid tumors.
• Understanding shear stress effects on endothelial immunobiology is crucial for targeted immunotherapy development.