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Immunosuppressive effect of shedding intercellular adhesion molecule 1 antigen on cell-mediated cytotoxicity against
1Department of Internal Medicine, University of Tsukuba, Ibaraki.
Insights
Tumor cells shed intercellular adhesion molecule-1 (ICAM-1) to inhibit cytotoxic LAK cell activity. This shedding interferes with the LFA-1/ICAM-1 interaction, reducing the immune cells' ability to kill tumor cells.
Area of Science:
- Immunology
- Cell Biology
- Cancer Research
Background:
- Intercellular adhesion molecule-1 (ICAM-1) plays a role in immune cell interactions.
- Leukocyte function-associated antigen-1 (LFA-1) on effector cells binds to ICAM-1 on target cells.
- Tumor cells can shed antigens, potentially influencing immune responses.
Purpose of the Study:
- To investigate if shedding of ICAM-1 from tumor cells inhibits the LFA-1/ICAM-1 interaction.
- To determine the effect of shed ICAM-1 on cytotoxic effector cell activity against tumor cells.
Main Methods:
- Cultured tumor cells, including interferon-gamma-stimulated cells, were used to generate spent media.
- Lymphokine-activated killer (LAK) cells were incubated with spent media containing shed ICAM-1.
- The cytotoxic activity of LAK cells was measured against ICAM-1+ target tumor cells.
Main Results:
- LAK cell cytotoxic activity was significantly decreased when incubated with spent media from ICAM-1+ tumor cells, particularly those stimulated with interferon-gamma.
- Treatment with spent media from ICAM-1- tumor cells did not significantly reduce LAK cell activity.
- Shed ICAM-1 appears to interfere with the binding of LFA-1 on LAK cells.
Conclusions:
- Shedding of ICAM-1 antigen by tumor cells can inhibit the interaction between LFA-1 on cytotoxic effector cells and ICAM-1 on target tumor cells.
- This shedding mechanism leads to reduced cytotoxic activity of LAK cells against tumors.
- ICAM-1 shedding represents a potential immune evasion strategy for tumors.
Abstract:
We have examined whether shedding intercellular adhesion molecule-1 (ICAM-1) antigen from cultured tumors is able to inhibit the leukocyte function-associated antigen-1 (LFA-1)/ICAM-1 interaction between cytotoxic effector cells and ICAM-1+ target tumor cells. The cytotoxic activity of lymphokine-activated killer (LAK) cells incubated with spent media from ICAM-1+ tumor cells, especially interferon-gamma-stimulated tumor cells, was significantly decreased as compared with that of LAK cells treated with fresh culture medium without ICAM-1 antigen. Treatment of LAK cells with spent media from ICAM-1- tumor cells did not cause a significant decrease of the cytolytic activity towards ICAM-1+ tumor cells. These findings suggest that shedding of ICAM-1 antigen could be involved in binding of LFA-1 to LAK cells, resulting in reduced cytolytic activity.