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Updated: Aug 8, 2026
Static Adhesion Assay for the Study of Integrin Activation in T Lymphocytes
Published on: June 13, 2014
Constitutive absence and interferon-gamma-induced expression of adhesion molecules in basal cell carcinoma
R S Taylor1, C E Griffiths, M D Brown
1Department of Dermatology, University of Michigan Medical School.
Insights
Basal cell carcinomas (BCCs) often lack crucial adhesion molecules like ICAM-1 and LFA-3, hindering immune cell detection. However, these molecules can be induced by interferon-gamma, suggesting a potential therapeutic target for BCCs.
Area of Science:
- Immunology
- Dermatology
- Oncology
Background:
- Lymphocyte adhesion to target cells is vital for immune responses, mediated by molecules like lymphocyte function-associated (LFA) antigens and their ligands.
- Intercellular adhesion molecule-1 (ICAM-1) and LFA-3 are key adhesion molecules expressed on nonlymphoid cells, critical for lymphocyte binding.
Purpose of the Study:
- To investigate whether basal cell carcinomas (BCCs) evade immune detection by lacking adhesion molecules necessary for cytotoxic T lymphocyte binding.
- To examine the expression of ICAM-1 and LFA-3 on BCCs and their modulation by interferon-gamma (IFN-gamma).
Main Methods:
- Analysis of ICAM-1 and LFA-3 expression on freshly excised invasive BCCs.
- Assessment of adhesion molecule expression on BCCs before and after in vitro incubation with IFN-gamma.
- Examination of ICAM-1 expression on overlying normal keratinocytes in relation to dermal lymphocytic infiltrate.
Main Results:
- A high percentage of BCCs (93%) lacked ICAM-1 expression, and a significant portion (73%) lacked LFA-3 expression.
- Normal overlying keratinocytes expressed ICAM-1, especially when accompanied by a lymphocytic infiltrate.
- In vitro IFN-gamma treatment induced ICAM-1 expression on 85% of BCC tumors studied.
Conclusions:
- The constitutive absence of ICAM-1 and LFA-3 on BCCs is a potential mechanism for immune evasion.
- BCC cells have the capacity to express these adhesion molecules, suggesting that low in vivo cytokine levels or barriers to cytokine interaction may be responsible for their absence.
- IFN-gamma can induce the expression of these critical adhesion molecules on BCCs, highlighting a potential therapeutic strategy.
Abstract:
Adhesion of lymphocytes to target cells via certain cell surface molecules is important in cytotoxic T lymphocyte-mediated immune reactions. The binding of lymphocyte function-associated (LFA) antigens 1 and 2, with their respective ligands, intercellular adhesion molecule-1 (ICAM-1) and LFA-3, which are expressed on the surface of nonlymphoid cells, has been shown to be critical for lymphocyte adhesion. To determine whether basal cell carcinomas (BCCs) can escape immunodetection as a result of the inability of cytotoxic T lymphocytes to bind tumor cells, the expression of adhesion molecules on numerous BCCs, before and after exposure to interferon-gamma (IFN-gamma), was examined. Ninety-three percent of 30 freshly excised invasive BCCs did not express ICAM-1 and 73% of 11 BCCs did not express LFA-3. However, the normal-appearing basal keratinocytes in epidermis overlying nests of BCC, did express ICAM-1, particularly when a marked LFA-1+ and LFA-2+ dermal lymphocytic infiltrate was present. After BCC tissue was incubated in vitro with IFN-gamma the expression of ICAM-1 was induced on 85% of tumors studied. Thus tumor cells did not possess an absolute inability to express adhesion molecules; rather the constitutive absence of such molecules may be due to insufficient in vivo cytokine levels necessary to induce expression or a barrier preventing cytokines from reaching and interacting with tumor cells. We conclude that the absence of ICAM-1 and LFA-3 adhesion molecules is a mechanism by which BCCs can avoid immunosurveillance.
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