Integrin αE(CD103)β7 in Epithelial Cancer

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 αE(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 αE(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 αE(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 αE(CD103)β7 expressing cells in these neoplasms. Given this background, we describe here that αE(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 αE(CD103)β7 in the tumor context is still far from clear. Here, we summarize the essential current knowledge on αE(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.

The prognostic significance of tumor-immune microenvironment in ascites of patients with high-grade serous carcinoma

“…CD103 is a subunit of the αE/β7 integrin that helps to retain expressing cells on the epithelium. 24 CD103 has been proposed as a marker of activated and tumorreactive CD8 + T cells in ascites HGSC 25,26 but no data correlated with survival was given. We showed that CD103 was mostly expressed on CD8 + , and not on CD4 + subsets, which was shown by us and by two other studies.…”

Phenotypic and Histological Distribution Analysis Identify Mast Cell Heterogeneity in Non-Small Cell Lung Cancer

“…CD103 (αE)β7 integrin binds to E-cadherin expressed by epithelial cells. The CD103 role is well known to allow CD103 + tissue-resident memory T cells to adhere to epithelial cells and reside in tissues [33]. In cancer, CD8 + CD103 + TIL participate in tumor cell killing and cytokine production within the TME [34].…”

Epithelial–Mesenchymal Transition in Acute Leukemias

“…On the other hand, E-cadherin found in epithelial cells also interacts with some surface markers found on some subsets of T cells to modulate the immune system [71]. E-cadherin has been shown to interact with CD103 found on cytotoxic T lymphocytes (CTLs) and tissue-resident T lymphocytes (TREMs), activating the cytotoxic functions of these cells in a TCR-dependent manner [72,73]. E-cadherin also interacts with killer cell lectin-like receptor G1 (KLRG1) on the surface of NK and CD8+ cells, inhibiting TCR signaling and thus the effector functions of these cells [74][75][76].…”