Departments of Pathology.
Obstetrics and Gynecology.
J Immunother. 2021 Jan;44(1):22-28. doi: 10.1097/CJI.0000000000000343.
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.
结直肠癌（CRC）是全球第三大常见恶性肿瘤。新型免疫检查点 V 结构域免疫球蛋白抑制 T 细胞激活（VISTA）已成为癌症治疗的有前途的靶点；然而，其在 CRC 中的表达的预后意义尚不清楚。在这项研究中，使用免疫组织化学染色法在来自 1434 名 I-III 期 CRC 患者的组织微阵列中研究了 VISTA 的表达情况（探索队列中 816 名，验证队列中 618 名）。VISTA 蛋白分别在肿瘤细胞和肿瘤浸润免疫细胞（ICs）中进行评估。分析了 VISTA 表达、错配修复（MMR）状态与临床病理参数之间的关系，以及 VISTA 对生存的影响。在 N0 期、T1-2 期、低肿瘤分级、高 CD8 密度和 MMR 缺陷型肿瘤患者中，IC 上的高 VISTA 表达（即，≥5%的染色）更为常见，并且与 CRC 患者的生存延长呈正相关。高 VISTA 表达是独立于临床病理参数和 MMR 状态的生存延长的显著预测因子。总体而言，我们的结果表明，肿瘤浸润性 IC 上的高 VISTA 表达与早期肿瘤分期、MMR 缺乏和 CRC 患者的良好预后相关。这应该在未来针对 CRC 患者的 VISTA 调节免疫治疗试验中得到考虑。
