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Soluble intercellular adhesion molecule-1 inhibits MHC-restricted specific T cell/tumor interaction
J C Becker1, C Termeer, R E Schmidt
1Department of Dermatology, University of Würzburg, Germany.
Insights
Soluble intercellular adhesion molecule-1 (ICAM-1) inhibits T cell-mediated melanoma killing and cytokine production. This soluble ICAM-1 blocks specific T cell interactions with melanoma, impacting immune responses.
Area of Science:
- Immunology
- Cell Biology
- Oncology
Background:
- Intercellular adhesion molecule-1 (ICAM-1)/LFA-1 pathway is crucial for immune cell adhesion and function.
- Soluble ICAM-1 has previously shown inhibitory effects on non-MHC-restricted cytotoxicity.
Purpose of the Study:
- To investigate the impact of soluble ICAM-1 on MHC-restricted T cell interactions with melanoma.
- To characterize the role of soluble ICAM-1 in T cell-mediated tumor immunity.
Main Methods:
- Established tumor-infiltrating lymphocyte (TIL) clones and autologous melanoma lines.
- Assessed conjugate formation and MHC-restricted killing of melanoma by TIL clones.
- Evaluated the effects of purified soluble ICAM-1 and melanoma supernatants on TIL/melanoma interactions.
Main Results:
- Purified soluble ICAM-1 and melanoma-derived soluble ICAM-1 significantly inhibited TIL-melanoma conjugate formation.
- Soluble ICAM-1 abrogated MHC-restricted killing of melanoma by TIL clones.
- Soluble ICAM-1 blocked the induction of cytokines in TILs upon contact with autologous tumor cells.
Conclusions:
- Soluble ICAM-1 effectively inhibits MHC-restricted T cell-mediated killing of melanoma.
- Soluble ICAM-1 interferes with T cell-tumor cell interactions and subsequent immune responses.
- Targeting soluble ICAM-1 may represent a therapeutic strategy in melanoma treatment.
Abstract:
Intercellular adhesion molecule-1 (ICAM-1)/LFA-1-mediated cell-cell adhesion is essential for various immunologic functions. It was previously shown that some of these, including non-MHC-restricted cytotoxicity, could be inhibited by soluble forms of ICAM-1. Here, we characterize the effects of soluble ICAM-1 on MHC-restricted specific T cell/melanoma interactions. Tumor-infiltrating lymphocyte (TIL) clones, as well as melanoma lines from the same tumor specimens, were established. The TIL clones used were able to form conjugates with the autologous tumor and to kill it in an MHC-restricted way. TIL/melanoma interaction also induced increased cytokine production in TIL. Using this system, we could demonstrate that purified soluble ICAM-1 (950 ng/ml) or 12-fold concentrated cell-free melanoma supernatants, containing shed ICAM-1 (1000 ng/ml), were able to inhibit conjugate formation between T cell clones and the autologous melanoma cells as efficiently as mAb against CD11a. In addition, free ICAM-1 abrogated the MHC-restricted killing of the melanoma exerted by T cell clones and blocked the induction of cytokines in T cells due to the contact with autologous tumor cells.
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