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Soluble intercellular adhesion molecule-1 and natural killer cell activity in gastric cancer patients
A Kaihara1, H Iwagaki, A Gouchi
1First Department of Surgery, Okayama University Medical School, Japan.
Insights
Elevated soluble intercellular adhesion molecule-1 (sICAM-1) and anti-ICAM-1 antibodies suppress immune function in gastric cancer patients. These factors inhibit the ICAM-1/LFA-1 system, impacting natural killer cell activity and metastasis.
Area of Science:
- Immunology
- Oncology
Background:
- Intercellular adhesion molecule-1 (ICAM-1) and leukocyte function antigen-1 (LFA-1) mediate immune cell interactions.
- Soluble ICAM-1 (sICAM-1) circulates in the blood and can interfere with cell-surface ICAM-1 binding.
Purpose of the Study:
- To investigate the role of sICAM-1 and anti-ICAM-1 monoclonal antibodies in gastric cancer immunity.
- To assess the impact of these factors on natural killer (NK) cell activity and cancer metastasis.
Main Methods:
- Serum levels of sICAM-1 were measured in gastric cancer patients and healthy controls.
- NK cell activity was assessed using peripheral blood mononuclear cells (PBMCs) and K562 target cells.
- The effect of anti-ICAM-1 monoclonal antibody on NK activity and experimental liver metastasis in mice was evaluated.
Main Results:
- Serum sICAM-1 levels were significantly elevated in gastric cancer patients.
- Serum from advanced gastric cancer patients decreased NK activity.
- Anti-ICAM-1 monoclonal antibody inhibited NK activity in cancer patients and increased metastasis in a mouse model.
Conclusions:
- Both sICAM-1 and anti-ICAM-1 monoclonal antibodies exhibit immunosuppressive effects in gastric cancer.
- These factors likely inhibit the ICAM-1/LFA-1 system, contributing to immune evasion and potentially promoting metastasis.
Abstract:
Intercellular adhesion molecule-1 (ICAM-1), a molecule bound to the cell surface, is a ligand for leukocyte function antigen-1 (LFA-1), and the ICAM-1/LFA-1 system mediates various cell-cell interactions involved in immunity. Soluble ICAM-1 (sICAM-1) is a circulating substance and binds with LFA-1 of leukocytes, thus, making leukocytes less available for binding with cell surface ICAM-1 on target cells. The serum level of soluble ICAM-1 (sICAM-1) was found to be significantly elevated (p<0.01) in patients with early and advanced gastric cancer compared with healthy controls. Natural killer activity (NK activity) was assessed by measuring the cytotoxicity of peripheral blood mononuclear cells (PBMCs) for K562 cells. There was no significant difference in NK activity between gastric cancer patients and healthy controls when heat-inactivated fetal calf serum was used in assays. However, addition of patient serum significantly decreased (p<0.05) NK activity when the serum was from patients with advanced gastric cancer compared with healthy volunteers. Addition of anti-ICAM-1 monoclonal antibody 0 to 5.0 microg/ml caused little change in NK activity in healthy controls, but its addition at 10 microg/ml remarkably decreased NK-activity in gastric cancer patients, probably through antibody binding with ICAM-1 on target cells. In other experiments, liver metastasis was induced in mice by inoculation of colon 26 murine colon cancer cells. In vitro pretreatment of colon 26 cells with the anti-ICAM-1 monoclonal antibody significantly increased the number of metastatic nodules. These results suggest that both sICAM-1 and anti-ICAM-1 monoclonal antibody act as immunosuppressive factors by inhibiting the ICAM-1/LFA-1 system.