Department of Biochemistry and Molecular Biology, School of Medicine, and.
Institut de Neurociències, Universitat Autònoma de Barcelona, Bellaterra, Cerdanyola del Vallès, Barcelona, Spain.
JCI Insight. 2018 Sep 20;3(18). doi: 10.1172/jci.insight.120757.
Since the proper activation of T cells requires the physical interaction with target cells through the formation of immunological synapses (IS), an alteration at this level could be a reason why tumors escape the immune response. As part of their life cycle, it is thought that T cells alternate between a static phase, the IS, and a dynamic phase, the immunological kinapse (IK), depending on high or low antigen sensing. Our investigation performed in tissue samples of human glioma shows that T cells are able to establish synapsing interactions not only with glioma tumorigenic cells, but also with stromal myeloid cells. Particularly, the IS displaying a T cell receptor-rich (TCR-rich) central supramolecular activation cluster (cSMAC) is preferentially established with stromal cells, as opposed to malignant cells. Conversely, T cells in the malignant areas showed distinct morphometric parameters compared with nonneoplastic tissue - the former characterized by an elongated shape, well-suited to kinaptic dynamics. Importantly, high-resolution 3-dimensional analyses demonstrated the existence of bona-fide IK preferentially arranged in malignant areas of the tumor. This imbalance of IS/IK states between these 2 microenvironments reveals the low antigenic sensing of T cells when patrolling tumorigenic cells and reflects the immunoevasive environment of the tumor.
由于 T 细胞的适当激活需要通过形成免疫突触（IS）与靶细胞进行物理相互作用，因此这种水平的改变可能是肿瘤逃避免疫反应的原因之一。在它们的生命周期中，人们认为 T 细胞在静态阶段（IS）和动态阶段（IK）之间交替，这取决于高或低的抗原感应。我们在人类神经胶质瘤组织样本中的研究表明，T 细胞不仅能够与神经胶质瘤肿瘤细胞建立突触相互作用，还能够与基质髓样细胞建立突触相互作用。特别是，具有 T 细胞受体丰富（TCR-rich）中央超分子激活簇（cSMAC）的 IS 优先与基质细胞而不是恶性细胞建立。相反，与非肿瘤组织相比，恶性区域的 T 细胞表现出不同的形态计量参数——前者的特点是形状细长，非常适合动力学。重要的是，高分辨率 3 维分析表明，在肿瘤的恶性区域存在真正的 IK 优先排列。这两种微环境之间的 IS/IK 状态的不平衡揭示了 T 细胞在巡逻肿瘤细胞时对低抗原的感应，并反映了肿瘤的免疫逃避环境。
