Department of Pathology, Yonsei University College of Medicine, Seoul, Korea.
Mod Pathol. 2020 Feb;33(2):263-270. doi: 10.1038/s41379-019-0328-3. Epub 2019 Jul 30.
Malignant mesothelioma is a highly lethal cancer. V-set immunoregulatory receptor (VSIR, also known as V-domain Ig suppressor T-cell activation, VISTA), a negative immune checkpoint regulator, was reported to be expressed in malignant mesothelioma; however, its detailed expression pattern and clinicopathological significance have not been elucidated. We examined the expression of VSIR and CD274 and CD8 tumor-infiltrating lymphocytes in a total of 124 samples from 66 patients with malignant mesothelioma and analyzed the clinicopathological characteristics and their relationship with the immunohistochemical findings. A total of 553 non-small cell lung carcinomas were also evaluated for VSIR expression. VSIR expression was higher in epithelioid type mesothelioma (p < 0.001), whereas CD274 expression was higher in sarcomatoid type (p < 0.001). CD8 tumor-infiltrating lymphocytes were more abundant in sarcomatoid mesotheliomas (p < 0.001), VSIR-low tumors (p = 0.045), and CD274-high tumors (p < 0.001). VSIR and CD274 were differentially expressed in each histological component of the biphasic type. VSIR expression was associated with favorable survival (p = 0.008). Two patients with VSIR-high tumors had received pembrolizumab; however, they showed progressive disease. No VSIR expression was observed in tumor cells of non-small cell lung carcinomas. In conclusion, VSIR expression may define a unique class of mesothelioma, characterized by predominantly epithelioid type and favorable prognosis. VSIR expression may be used as an immunohistochemical diagnostic marker for epithelioid mesothelioma. CD274 expression was associated with sarcomatoid mesothelioma and high infiltration of CD8 lymphocytes. Because VSIR is a negative immune regulator and expressed in malignant mesothelioma, further study is warranted to investigate the therapeutic significance of VSIR blockade in this deadly cancer.
恶性间皮瘤是一种高度致命的癌症。V -set 免疫调节受体（VSIR，也称为 V 域 Ig 抑制性 T 细胞激活，VISTA）是一种负性免疫检查点调节剂，据报道在恶性间皮瘤中表达；然而，其详细的表达模式和临床病理意义尚未阐明。我们检查了总共 66 名恶性间皮瘤患者的 124 个样本中的 VSIR 和 CD274 及 CD8 肿瘤浸润淋巴细胞的表达，并分析了临床病理特征及其与免疫组织化学发现的关系。还评估了总共 553 例非小细胞肺癌的 VSIR 表达。上皮样型间皮瘤的 VSIR 表达更高（p<0.001），而肉瘤样型的 CD274 表达更高（p<0.001）。CD8 肿瘤浸润淋巴细胞在肉瘤样间皮瘤中更为丰富（p<0.001），VSIR 低肿瘤（p=0.045）和 CD274 高肿瘤（p<0.001）。VSIR 和 CD274 在双相型的每种组织学成分中均有差异表达。VSIR 表达与良好的生存相关（p=0.008）。两名 VSIR 高肿瘤患者接受了 pembrolizumab 治疗；然而，他们的病情出现了进展。非小细胞肺癌的肿瘤细胞中未观察到 VSIR 表达。总之，VSIR 表达可能定义了一类独特的间皮瘤，其特征为主要为上皮样型和良好的预后。VSIR 表达可用作上皮样间皮瘤的免疫组织化学诊断标志物。CD274 表达与肉瘤样间皮瘤和 CD8 淋巴细胞的高浸润相关。由于 VSIR 是一种负性免疫调节剂并在恶性间皮瘤中表达，因此需要进一步研究以探讨 VSIR 阻断在这种致命癌症中的治疗意义。
