Hoffmann Johanna C, Schön Michael P
Department of Dermatology, Venereology and Allergology, University Medical Center Göttingen, 37075 Göttingen, Germany.
Lower Saxony Institute of Occupational Dermatology, University Medical Center Göttingen, 37075 Göttingen, Germany.
Cancers (Basel). 2021 Dec 9;13(24):6211. doi: 10.3390/cancers13246211.
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 CD8T 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(CD103)β 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(CD103)β/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(CD103)β 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(CD103)β expressing cells in these neoplasms. Given this background, we describe here that α(CD103)β 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(CD103)β in the tumor context is still far from clear. Here, we summarize the essential current knowledge on α(CD103)β and outline that it is worthwhile to further explore this intriguing receptor with regard to the pathophysiology, therapy, and prognosis of solid tumors.
先天免疫系统和适应性免疫系统与肿瘤的相互作用十分复杂,常常以意想不到的方式影响病程和治疗。基于CD8T细胞可介导重要抗肿瘤作用这一概念,目前有几种疗法旨在增强其特异性活性。表达α(CD103)β整合素的CD8组织驻留T淋巴细胞亚群引起了特别关注。该受体可能通过与其配体E-钙黏蛋白相互作用,促进肿瘤浸润免疫细胞的募集和滞留。它似乎具有调节功能,被认为是某些免疫突触的组成部分。在富含转化生长因子的环境中,α(CD103)β/E-钙黏蛋白相互作用增强了肿瘤细胞与浸润性T淋巴细胞之间的结合强度。这种活性促进了溶细胞颗粒内容物和细胞因子的释放,以及进一步的免疫反应和靶细胞的杀伤。α(CD103)β在某些肿瘤中的表达与相对较好的预后相关,皮肤鳞状细胞癌可能是个明显的例外。尽管上皮性皮肤肿瘤是白种人最常见的肿瘤,但关于这些肿瘤中表达α(CD103)β的细胞分布的研究却很少。在此背景下,我们在此描述α(CD103)β在基底细胞癌中几乎不存在,但在鳞状细胞癌中更为丰富且分布不均。尽管有大量研究,但α(CD103)β在肿瘤环境中的作用仍远未明确。在此,我们总结了目前关于α(CD103)β的基本认识,并概述了就实体瘤的病理生理学、治疗和预后进一步探索这一有趣受体是值得的。