Department of Histology and Embryology, Department of Human Morphology and Embryology, Wroclaw Medical University, Chalubinskiego 6a, 50-368, Wroclaw, Poland.
Department of Pathology, Polish Mother's Memorial Hospital Research Institute, 93-338, Lodz, Poland.
Cancer Immunol Immunother. 2024 Jun 4;73(8):136. doi: 10.1007/s00262-024-03701-w.
A checkpoint protein called the V-domain Ig suppressor of T cell activation (VISTA) is important for controlling immune responses. Immune cells that interact with VISTA have molecules, or receptors, known as VISTA receptors. Immune system activity can be modified by the interaction between VISTA and its receptors. Since targeting VISTA or its receptors may be beneficial in certain conditions, VISTA has been studied in relation to immunotherapy for cancer and autoimmune illnesses. The purpose of this study was to examine the expression levels and interactions between VISTA and its receptors, VSIG3 and PSGL-1, in breast cancer tissues. IHC analysis revealed higher levels of proteins within the VISTA/VSIG3/PSGL-1 axis in cancer tissues than in the reference samples (mastopathies). VISTA was found in breast cancer cells and intratumoral immune cells, with membranous and cytoplasmic staining patterns. VISTA was also linked with pathological grade and VSIG3 and PSGL-1 levels. Furthermore, we discovered that the knockdown of one axis member boosted the expression of the other partners. This highlights the significance of VISTA/VSIG3/PSGL-1 in tumor stroma and microenvironment remodeling. Our findings indicate the importance of the VISTA/VSIG3/PSGL-1 axis in the molecular biology of cancer cells and the immune microenvironment.
一种名为 T 细胞活化的 V 结构域免疫球蛋白抑制因子（VISTA）的检查点蛋白对于控制免疫反应很重要。与 VISTA 相互作用的免疫细胞具有称为 VISTA 受体的分子或受体。VISTA 与其受体之间的相互作用可以修饰免疫系统的活性。由于靶向 VISTA 或其受体在某些情况下可能是有益的，因此已经研究了 VISTA 与癌症和自身免疫性疾病的免疫疗法的关系。本研究的目的是检查乳腺癌组织中 VISTA 与其受体 VSIG3 和 PSGL-1 之间的表达水平和相互作用。免疫组化分析显示，癌症组织中 VISTA/VSIG3/PSGL-1 轴内的蛋白水平高于参考样本（乳腺病）。在乳腺癌细胞和肿瘤内免疫细胞中发现了 VISTA，其染色模式为膜和细胞质。VISTA 还与病理分级以及 VSIG3 和 PSGL-1 水平相关。此外，我们发现一个轴成员的敲低会增强其他伙伴的表达。这突显了 VISTA/VSIG3/PSGL-1 在肿瘤基质和微环境重塑中的重要性。我们的研究结果表明 VISTA/VSIG3/PSGL-1 在癌细胞的分子生物学和免疫微环境中具有重要意义。
