| Summary: | 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<sup>+</sup>T cells can mediate important antitumor effects, several therapies now aim to amplify their specific activity. A subpopulation of CD8<sup>+</sup> tissue-resident T lymphocytes that express the α<sub>E</sub>(CD103)β<sub>7</sub> 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<sub>E</sub>(CD103)β<sub>7</sub>/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<sub>E</sub>(CD103)β<sub>7</sub> 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<sub>E</sub>(CD103)β<sub>7</sub> expressing cells in these neoplasms. Given this background, we describe here that α<sub>E</sub>(CD103)β<sub>7</sub> 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<sub>E</sub>(CD103)β<sub>7</sub> in the tumor context is still far from clear. Here, we summarize the essential current knowledge on α<sub>E</sub>(CD103)β<sub>7</sub> and outline that it is worthwhile to further explore this intriguing receptor with regard to the pathophysiology, therapy, and prognosis of solid tumors.
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