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全面免疫组化分析在胰胆管肿瘤中的预后标志物。

Comprehensive immunoprofile analysis of prognostic markers in pancreaticobiliary tract cancers.

机构信息

Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.

Medical Research Institute, Sungkyunkwan University School of Medicine, Seoul, South Korea.

出版信息

Cancer Med. 2023 Apr;12(7):7748-7761. doi: 10.1002/cam4.5530. Epub 2023 Jan 17.

Abstract

Pancreaticobiliary tract cancer has a poor prognosis with unmet needs in a new target treatment. Some studies have reported that an enhancement of T-cell immunity is associated with a good prognosis. The aim of this study is to investigate the immunoprofile as a prognostic marker of pancreaticobiliary tract cancers. Unresectable pancreatic ductal adenocarcinoma (PDAC, n = 80) and biliary tract cancer (BTC, n = 74) diagnosed between January 2012 and December 2018 in Samsung Medical Center were analyzed. Expression levels of CD8, FOXP3, PD-1, PD-L1, and CXCL13 in PDAC and BTC tissue samples were examined with immunohistochemical staining, which was evaluated with various clinical factors. In PDAC, higher degree of PD-L1 expression was significantly associated with shorter overall survival (OS) (p = 0.0095). On the other hand, higher infiltrations of PD-1 immune cells (p = 0.0002) and CD8 T cells (p = 0.0067) were associated with longer OS. In BTC, higher FOXP3 (p = 0.0343) and CD8 (p = 0.0028) cell infiltrations were associated with better survival. Low infiltration of CD8 (p = 0.0148), FOXP3 (p = 0.0208), PD-1 (p = 0.0318) cells in PDAC, and FOXP3 cells (p = 0.005) in BTC were considerably related to metastasis. In a combined evaluation of clinical factors and immunoprofiles, univariate analysis revealed that operation after chemotherapy (p < 0.0001), mass size (p = 0.0004), metastasis (p = 0.006), PD-L1 (p < 0.0001), PD-1 (p = 0.003) and CD8 (p = 0.0063) was significantly associated with OS in PDAC, and CD8 (p = 0.007) was statistically related to OS in BTC. In multivariate analysis, prognostic factors were operation after chemotherapy (p = 0.021) in PDAC and CD8 (p = 0.037) in BTC. Therefore, immunoprofile analysis of cells expressing CD8, FOXP3, PD-1, and PD-L1 might have prognostic values in patients with pancreaticobiliary tract cancers.

摘要

胰腺癌和胆管癌的预后较差,新的治疗靶点存在未满足的需求。一些研究报告称,T 细胞免疫增强与良好的预后相关。本研究旨在探讨作为胰腺癌和胆管癌预后标志物的免疫组化特征。分析了 2012 年 1 月至 2018 年 12 月在三星医疗中心诊断的不可切除的胰腺导管腺癌(PDAC,n=80)和胆管癌(BTC,n=74)。使用免疫组织化学染色检查 PDAC 和 BTC 组织样本中 CD8、FOXP3、PD-1、PD-L1 和 CXCL13 的表达水平,并结合各种临床因素进行评估。在 PDAC 中,较高程度的 PD-L1 表达与较短的总生存期(OS)显著相关(p=0.0095)。另一方面,较高水平的 PD-1 免疫细胞(p=0.0002)和 CD8 T 细胞浸润(p=0.0067)与较长的 OS 相关。在 BTC 中,较高的 FOXP3(p=0.0343)和 CD8(p=0.0028)细胞浸润与更好的生存相关。PDAC 中 CD8(p=0.0148)、FOXP3(p=0.0208)、PD-1(p=0.0318)细胞浸润和 BTC 中 FOXP3 细胞浸润(p=0.005)较低与转移密切相关。在对临床因素和免疫组化特征的单因素分析中,发现化疗后手术(p<0.0001)、肿块大小(p=0.0004)、转移(p=0.006)、PD-L1(p<0.0001)、PD-1(p=0.003)和 CD8(p=0.0063)与 PDAC 的 OS 显著相关,BTC 中 CD8(p=0.007)与 OS 相关。多因素分析显示,PDAC 的预后因素是化疗后手术(p=0.021),BTC 的预后因素是 CD8(p=0.037)。因此,表达 CD8、FOXP3、PD-1 和 PD-L1 的细胞免疫组化分析可能对胰腺癌和胆管癌患者具有预后价值。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d961/10134292/b845a83668bd/CAM4-12-7748-g004.jpg

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