利用数字图像分析探究小肠腺癌的免疫微环境。
Exploring the immune microenvironment in small bowel adenocarcinoma using digital image analysis.
发表日期:2023
作者:
Fatima Abdullahi Sidi, Victoria Bingham, Stephen McQuaid, Stephanie G Craig, Richard C Turkington, Jacqueline A James, Matthew P Humphries, Manuel Salto-Tellez
来源:
Cell Death & Disease
摘要:
小肠腺癌(SBA)是小肠罕见的恶性肿瘤,与晚期诊断和生存结局不良相关。高表达的免疫细胞和免疫检查点生物标志物,特别是程序性细胞死亡配体-1(PD-L1),已被证明对疾病进展有显著影响。我们对一组SBA患者的免疫细胞和免疫检查点生物标志物的表达进行了分析,并评估了它们对无进展生存(PFS)和总生存(OS)的影响。我们获得了25个患者样本,以甲醛固定、石蜡包埋(FFPE)的组织形式,制备成组织微阵列(TMAs)。使用经验证的CD3、CD4、CD8、CD68、PD-L1、ICOS、IDO1和LAG3抗体进行自动免疫组化(IHC)染色。幻灯片进行数字化扫描,并使用开源图像分析软件QuPath进行生物标志物密度和阳性率的评估。使用Kaplan Meier方法进行生存分析。记录了生物标志物的不同表达情况。高表达的CD3、CD4和IDO1对PFS具有显著意义(P分别为0.043、0.020和0.018)。ICOS的高表达对PFS(P = 0.040)和OS(P = 0.041)都有显著意义,而肿瘤细胞中PD-L1的高表达对OS具有显著意义(P = 0.033)。观察到PD-L1和IDO1之间存在高度相关性(Pearson相关系数为1),因此发现肿瘤细胞中IDO1的高表达对PFS(P = 0.006)和OS(P = 0.034)有显著意义。免疫细胞和免疫检查点蛋白的高水平对SBA患者的生存具有显著影响。这些数据可能为SBA患者的免疫治疗管理提供了洞察。版权所有:© 2023 Sidi et al. 本文是根据创作共享许可协议发布的开放获取文章,允许在任何媒介中不受限制地使用、分发和复制,前提是原始作者和来源得到了适当的认可。
Small bowel adenocarcinoma (SBA) is a rare malignancy of the small intestine associated with late stage diagnosis and poor survival outcome. High expression of immune cells and immune checkpoint biomarkers especially programmed cell death ligand-1 (PD-L1) have been shown to significantly impact disease progression. We have analysed the expression of a subset of immune cell and immune checkpoint biomarkers in a cohort of SBA patients and assessed their impact on progression-free survival (PFS) and overall survival (OS).25 patient samples in the form of formalin fixed, paraffin embedded (FFPE) tissue were obtained in tissue microarray (TMAs) format. Automated immunohistochemistry (IHC) staining was performed using validated antibodies for CD3, CD4, CD8, CD68, PD-L1, ICOS, IDO1 and LAG3. Slides were scanned digitally and assessed in QuPath, an open source image analysis software, for biomarker density and percentage positivity. Survival analyses were carried out using the Kaplan Meier method.Varying expressions of biomarkers were recorded. High expressions of CD3, CD4 and IDO1 were significant for PFS (p = 0.043, 0.020 and 0.018 respectively). High expression of ICOS was significant for both PFS (p = 0.040) and OS (p = 0.041), while high PD-L1 expression in tumour cells was significant for OS (p = 0.033). High correlation was observed between PD-L1 and IDO1 expressions (Pearson correlation co-efficient = 1) and subsequently high IDO1 expression in tumour cells was found to be significant for PFS (p = 0.006) and OS (p = 0.034).High levels of immune cells and immune checkpoint proteins have a significant impact on patient survival in SBA. These data could provide an insight into the immunotherapeutic management of patients with SBA.Copyright: © 2023 Sidi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.