Jiangsu Institute of Clinical Immunology & Jiangsu Key Laboratory of Clinical Immunology, The First Affiliated Hospital of Soochow University, Suzhou, China.
Department of Laboratory Medicine, The First People's Hospital of Taicang, Taicang Hospital Affiliated to Soochow University, Suzhou, China.
Int Immunopharmacol. 2021 Jan;90:107144. doi: 10.1016/j.intimp.2020.107144. Epub 2020 Nov 10.
Metastasis commonly occurs in colorectal cancer (CRC) patients and confers a poor prognosis. B7-H4, an immune checkpoint molecule, has been found to be expressed in numerous tumor tissues and play critical roles in tumor progression. However, B7-H4 expression and its prognostic significance in different metastases from CRC remain unclear. In the present study, we screened a novel mouse anti-human B7-H4 monoclonal antibody (mAb) which exhibited a higher degree of recognition and sensitivity than the commercial reagent in immunohistochemistry (IHC). Using this antibody, overall 110 metastatic and paired primary lesions of CRC were analyzed for their expression of B7-H4, CD8 and CD68. Our results showed that expression of B7-H4 and CD68 in metastastic lesions was significantly higher than that in matched primary lesions (P = 0.0016, P < 0.0001). We also found a significant increase of CD68-positive immune cell infiltration in the B7-H4 high expressing metastases (P = 0.041). Moreover, upregulated B7-H4 in metastatic lesions was correlated with poor prognosis of patients (P = 0.014), while in primary lesions, B7-H4 combined with CD8 was associated with the overall survival (OS) (P = 0.043). Further, B7-H4 expression in metastatic lesions was significantly correlated with hazard ratio (HR) both in univariate and multivariate analysis. Altogether, B7-H4 in metastatic lesions is promising to be a potential prognostic indicator of CRC, and may promote tumor progression and metastasis of this cancer.
转移通常发生在结直肠癌（CRC）患者中，并导致预后不良。B7-H4 是一种免疫检查点分子，已在许多肿瘤组织中发现，并在肿瘤进展中发挥关键作用。然而，B7-H4 在 CRC 不同转移部位的表达及其预后意义尚不清楚。在本研究中，我们筛选了一种新型的抗人 B7-H4 单克隆抗体（mAb），该抗体在免疫组织化学（IHC）中比商业试剂具有更高的识别度和灵敏度。使用该抗体，我们分析了 110 例 CRC 转移灶及其配对原发灶中 B7-H4、CD8 和 CD68 的表达。结果显示，转移灶中 B7-H4 和 CD68 的表达明显高于配对的原发灶（P=0.0016，P<0.0001）。我们还发现，B7-H4 高表达转移灶中 CD68 阳性免疫细胞浸润显著增加（P=0.041）。此外，转移灶中上调的 B7-H4 与患者预后不良相关（P=0.014），而在原发灶中，B7-H4 与 CD8 联合与总生存期（OS）相关（P=0.043）。进一步的，在单因素和多因素分析中，转移灶中 B7-H4 的表达与风险比（HR）显著相关。总的来说，转移灶中 B7-H4 有望成为 CRC 的潜在预后指标，并可能促进该癌症的肿瘤进展和转移。
