Department of General Surgery, Fujian Medical University Union Hospital, No. 29 Xinquan Road, Fuzhou, 350001, People's Republic of China.
The Cancer Center, Fujian Medical University Union Hospital, Fuzhou, 350001, China.
J Cancer Res Clin Oncol. 2021 Feb;147(2):517-531. doi: 10.1007/s00432-020-03463-9. Epub 2020 Nov 25.
V-domain Ig suppressor of T cell activation (VISTA) is a novel immune checkpoint protein that belongs to the B7 family. The aim of this study was to investigate the prognostic significance and therapeutic potential of VISTA in patients with pancreatic cancer.
Using immunohistochemistry (IHC), we examined the expression of VISTA and demonstrated the associations between the VISTA and overall survival in 223 PDAC patients from 2 different unrelated retrospective cohorts. The multiplex immunofluorescence was performed to illuminate the relationship between VISTA expression and tumor-infiltrating immune cell subclusters of PDAC. We also verified the findings in The Cancer Genome Atlas (TCGA) dataset. The anti-tumor effect of anti-VISTA therapy was studied by the mouse model with liver metastases of PDAC.
The VISTA protein was highly expressed in 25.6% of tumor cells (TCs), 38.1% of immune cells, and 26.0% of endothelial cells in 223 PDAC tumor tissues. VISTA expression in TCs was significantly associated with prolonged overall survival. Multiplex immunofluorescence analysis revealed that VISTA level was positively correlated with CD68 macrophages, CD3 T cells, and CD19 B cells in PDAC. However, a higher expression level of VISTA was detected in tumor-infiltrating CD68 macrophages than in CD3 T and CD19 B cells. Furthermore, anti-VISTA antibody treatment significantly reduced the number of metastatic nodules in livers of mouse models of PDAC with liver metastases.
VISTA expressed in TCs is associated with a favorable prognosis in PDAC. Moreover, immunotherapy with anti-VISTA antibodies may potentially be an effective treatment strategy against PDAC.
V 结构域免疫球蛋白抑制 T 细胞激活因子（VISTA）是一种新型免疫检查点蛋白，属于 B7 家族。本研究旨在探讨 VISTA 在胰腺癌患者中的预后意义和治疗潜力。
我们使用免疫组织化学（IHC）检测了 223 例来自 2 个独立回顾性队列的 PDAC 患者中 VISTA 的表达，并展示了 VISTA 与总生存期之间的关联。我们还进行了多重免疫荧光分析，以阐明 VISTA 表达与 PDAC 肿瘤浸润免疫细胞亚群之间的关系。我们在癌症基因组图谱（TCGA）数据库中验证了这些发现。通过 PDAC 肝转移的小鼠模型研究了抗 VISTA 治疗的抗肿瘤作用。
在 223 例 PDAC 肿瘤组织中，25.6%的肿瘤细胞（TCs）、38.1%的免疫细胞和 26.0%的内皮细胞高表达 VISTA 蛋白。TCs 中 VISTA 的表达与总生存期延长显著相关。多重免疫荧光分析显示，VISTA 水平与 PDAC 中的 CD68 巨噬细胞、CD3 T 细胞和 CD19 B 细胞呈正相关。然而，在肿瘤浸润的 CD68 巨噬细胞中检测到的 VISTA 表达水平高于 CD3 T 和 CD19 B 细胞。此外，抗 VISTA 抗体治疗显著减少了具有肝转移的 PDAC 小鼠模型中肝脏转移性结节的数量。
TCs 中表达的 VISTA 与 PDAC 的良好预后相关。此外，抗 VISTA 抗体的免疫疗法可能是一种针对 PDAC 的有效治疗策略。
