ICAM-1 is a cell-surface glycoprotein and a member of the immunoglobulin (Ig) protein superfamily. ICAM-1 mediates the interaction between keratinocytes and leukocytes. ICAM-1 facilitates a variety of both afferent and efferent immune responses that require intercellular contact and collaboration, including T helper responses, T-dependent B cell responses, antigen-induced T cell proliferation, cell-mediated cytotoxicity, and the binding of leukocytes to vascular endothelium prior to extravasation into inflamed tissue. Pro-inflammatory cytokines interferon-γ and TNF-α stimulate the expression of keratinocyte ICAM-1 and this up-regulation is blocked both in vivo and in vitro if keratinocytes are irradiated with UVB prior to cytokine treatment. In contrast, ICAM-2 is expressed primarily on endothelium and leukocytes (except neutrophils), and its expression generally is not responsive to cytokines. ICAM-3 predominates on thymocytes and resting lymphocytes, which are low in ICAM-1. When neutrophils are activated, they shed the majority of their ICAM-3 into the medium by proteolytic cleavage. In some reports, the expression of ICAM-1 has been positively correlated with a more aggressive tumor phenotype and metastatic potential. For instance, the invasiveness of breast cancer cells has been positively correlated with the expression of ICAM-1. Also, it has been suggested that an ICAM-1–ICAM-1 homophilic interaction between breast cancer cells and mesenchymal stem cells in bone marrow mediates the metastatic expansion of cancer cells, displacing hematopoietic stem cells from their niche.