High VISTA Expression Correlates With a Favorable Prognosis in Patients With Colorectal Cancer
High VISTA Expression Correlates With a Favorable Prognosis in Patients With Colorectal Cancer
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VISTA 高表达与结直肠癌患者的良好预后相关
DOI：
10.1097/cji.0000000000000343
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发表时间：
2021-01-01
影响因子：
3.9
通讯作者：
Chen, Jie
中科院分区：
文献类型：
--
作者：
Zong, Liju;Yu, Shuangni;Chen, Jie
补充数字内容可在正文中找到。结直肠癌(CRC)是世界上第三常见的恶性肿瘤。新的免疫检查点V结构域T细胞激活抑制因子(VistA)已成为肿瘤治疗的新靶点，但其在结直肠癌中的表达对预后的意义尚不清楚。在这项研究中，应用免疫组织化学染色方法研究了1434例I-III期结直肠癌患者组织芯片中VistA的表达(816例在探索性队列中，618例在验证队列中)。检测VistA蛋白在肿瘤细胞和肿瘤浸润性免疫细胞(IC)中的表达。分析Vista表达、错配修复(MMR)状态和临床病理参数之间的关系，以及Vista对生存率的影响。VistA高表达(即≥5%染色)在N0期、T1-2期、低分级、高密度和MMR缺乏的结直肠癌患者中更为常见，并与患者的生存时间呈正相关。Vista高表达是独立于临床病理参数和MMR状态的延长生存期的显著预测因素。总体而言，我们的结果表明，肿瘤浸润性IC上Vista的高表达与早期肿瘤分期、MMR缺陷和结直肠癌患者良好的预后相关。这一点应该在未来针对结直肠癌患者的Vista调节免疫疗法的试验中加以考虑。
Supplemental Digital Content is available in the text. Colorectal cancer (CRC) is the third most common malignancy worldwide. The novel immune checkpoint V-domain Ig suppressor of T-cell activation (VISTA) has emerged as a promising target for cancer treatment; however, the prognostic significance of its expression in CRC remains unknown. In this study, immunohistochemical staining was used to investigate VISTA expression in tissue microarrays from 1434 patients with stage I–III CRC (816 in the exploratory cohort and 618 in the validation cohort). VISTA protein was evaluated separately in tumor cells and tumor-infiltrating immune cells (ICs). The associations between VISTA expression, mismatch repair (MMR) status, and clinicopathologic parameters were analyzed, as was the effect of VISTA on survival. High VISTA expression on ICs (ie, ≥5% staining) was more frequent in patients with N0 stage, T1–2 stage, low tumor grade, high CD8 density, and MMR-deficient tumors, and was positively associated with prolonged survival in patients with CRC. High VISTA expression was a significant predictor of prolonged survival independent of clinicopathologic parameters and MMR status. Overall, our results indicate that high VISTA expression on tumor-infiltrating ICs correlates with early tumor stage, MMR deficiency, and a favorable prognosis in patients with CRC. This ought to be considered in future trials of VISTA-modulating immunotherapy for patients with CRC.