Integrin α_E(CD103)β₇ in Epithelial Cancer

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)β₇ 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)β₇/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)β₇ 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)β₇ expressing cells in these neoplasms. Given this background, we describe here that α_E(CD103)β₇ 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)β₇ in the tumor context is still far from clear. Here, we summarize the essential current knowledge on α_E(CD103)β₇ and outline that it is worthwhile to further explore this intriguing receptor with regard to the pathophysiology, therapy, and prognosis of solid tumors.