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