Integrin α(E)(CD103)β(7) in Epithelial Cancer

SIMPLE SUMMARY: The immune system in cancer is a central focus of research and clinical developments alike. We delineate our current view on α(E)(CD103)β(7) integrin (CD103) expressing tumor infiltrating T lymphocytes in epithelial tumors. CD103 binds to E-cadherin within epithelial tissues and can be induced by TGFβ. It appears to play a role in the formation and function of the immunological synapse between cytotoxic T cell and tumor cell. Infiltration of CD103-expressing T cells in epithelial tumors is often associated with a better prognosis for patients. An exception seems to be epithelial skin tumors, where CD103 expression is not associated with better prognosis. We also show new data that CD103 is significantly more highly expressed in squamous cell carcinomas of the skin than in basal cell carcinomas or some other skin tumors, although the overall expression pattern is heterogeneous. A better understanding of α(E)(CD103)β(7) integrin may facilitate some immunological antitumor therapies. ABSTRACT: Interactions of both the innate and the adaptive immune system with tumors are complex and often influence courses and therapeutic treatments in unanticipated ways. Based on the concept that CD8(+)T cells can mediate important antitumor effects, several therapies now aim to amplify their specific activity. A subpopulation of CD8(+) tissue-resident T lymphocytes that express the α(E)(CD103)β(7) integrin has raised particular interest. This receptor presumably contributes to the recruitment and retention of tumor-infiltrating immune cells through interaction with its ligand, E-cadherin. It appears to have regulatory functions and is thought to be a component of some immunological synapses. In TGF-rich environments, the α(E)(CD103)β(7)/E-cadherin-interaction enhances the binding strength between tumor cells and infiltrating T lymphocytes. This activity facilitates the release of lytic granule contents and cytokines as well as further immune responses and the killing of target cells. Expression of α(E)(CD103)β(7) in some tumors is associated with a rather favorable prognosis, perhaps with the notable exception of squamous cell carcinoma of the skin. Although epithelial skin tumors are by far the most common tumors of fair-skinned people, there have been very few studies on the distribution of α(E)(CD103)β(7) expressing cells in these neoplasms. Given this background, we describe here that α(E)(CD103)β(7) is scarcely present in basal cell carcinomas, but much more abundant in squamous cell carcinomas with heterogeneous distribution. Notwithstanding a substantial number of studies, the role of α(E)(CD103)β(7) in the tumor context is still far from clear. Here, we summarize the essential current knowledge on α(E)(CD103)β(7) and outline that it is worthwhile to further explore this intriguing receptor with regard to the pathophysiology, therapy, and prognosis of solid tumors.