Abstract
Simple SummaryThe immune system in cancer is a central focus of research and clinical developments alike. We delineate our current view on αE(CD103)β7 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 αE(CD103)β7 integrin may facilitate some immunological antitumor therapies.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.
Highlights
While transforming growth factor-β (TGFβ) conveys negative signals toward IL-1 and IL-2-dependent proliferation of activated T cells [37,38], B cells [39], and myeloid cells [40], it appears to play a key role for CD103-dependent immunity within tumor microenvironments [32,36]
Since TGFβ induces CD103 and suppresses LFA-1 within the tumor microenvironment [51], it is quite conceivable that, at least in some epithelial tumors, cytolysis by cytotoxic T lymphocytes (CTL) depends on the interaction between CD103 and E-cadherin within the synapses
Recent work suggests that CD103-expressing exosomes derived from tumor stem cells through miR that impair PTEN expression may promote epithelial–mesenchymal transition and metastasis of renal cancer cells and that these exosomes have a degree of organotropism [70]
Summary
The integrin αE chain (CD103 in the strict sense) dimerizes exclusively with the β7 integrin subunit (Figure 1) while the latter can pair with α4 , resulting in the α4 (CD49d) β7 receptor (lymphocyte Peyer’s patch adhesion molecule) [21,22]. EC1 domain of E-cadherin with the help of its MIDAS motif of the first extracellular domain This binding site is different from the one responsible for the homophilic binding of E-cadherin. The β7 chain does not bind directly to E-cadherin It facilitates intracellular signaling through its tail domain. Notwithstanding extensive attempts to identify factors that induce CD103, only transforming growth factor-β (TGFβ) has been found to consistently upregulate its expression, e.g., in human leukocyte cultures [32–34]. This cytokine induces CD103 on human CTLs in conjunction with T cell receptor (TCR) activation [35,36]. While TGFβ conveys negative signals toward IL-1 and IL-2-dependent proliferation of activated T cells [37,38], B cells [39], and myeloid cells [40], it appears to play a key role for CD103-dependent immunity within tumor microenvironments [32,36]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
