Hyperthermia increases intercellular adhesion molecule-1 expression and lymphocyte adhesion to endothelial cells

Area of Science:

• Immunology
• Oncology
• Biomedical Engineering

Background:

• Immunotherapy combined with whole-body hyperthermia shows efficacy against large tumors.
• The mechanism behind this synergy, particularly hyperthermia's effect on immune cell interactions, requires elucidation.
• Hypothesized that hyperthermia influences lymphocyte-endothelial cell adhesion.

Purpose of the Study:

• To investigate the impact of hyperthermia on lymphocyte-endothelial cell adhesion.
• To determine the role of intercellular adhesion molecule-1 (ICAM-1) in hyperthermia-induced adhesion.
• To compare the effects of hyperthermia, interferon-gamma (IFN-γ), and their combination on adhesion and ICAM-1 expression.

Main Methods:

• Utilized cultured human umbilical vein endothelial cells (HUVEC) and peripheral blood lymphocytes.
• Assessed lymphocyte adhesion to HUVEC treated with control, hyperthermia, IFN-γ, or combination therapy.
• Quantified cell surface and soluble ICAM-1 expression using flow cytometry and ELISA, respectively; evaluated the effect of anti-ICAM antibody.

Main Results:

• Hyperthermia and IFN-γ significantly increased lymphocyte adhesion to HUVEC.
• Combined hyperthermia and IFN-γ yielded the greatest increase in adhesion.
• Hyperthermia-induced adhesion was abrogated by anti-ICAM antibody, suggesting ICAM-1 mediation.
• Both cell surface and soluble ICAM-1 levels were elevated by hyperthermia and IFN-γ, with peak soluble levels at 24 hours.

Conclusions:

• Hyperthermia significantly enhances lymphocyte-endothelial cell adhesion, partly through ICAM-1.
• Increased ICAM-1 expression and release contribute to hyperthermia's effect on immune cell trafficking.
• These findings suggest a novel mechanism for hyperthermia in improving immunotherapy efficacy.