Precision Medicine Centre of Excellence, The Patrick G. Johnston Centre for Cancer Research, Queen's University Belfast, Antrim, United Kingdom.
Cellular Pathology, Belfast Health and Social Care Trust, Belfast City Hospital, Lisburn Road, Belfast, Antrim, United Kingdom.
PLoS One. 2023 Aug 1;18(8):e0289355. doi: 10.1371/journal.pone.0289355. eCollection 2023.
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.
小肠腺癌（SBA）是一种罕见的小肠恶性肿瘤，其诊断往往较晚，生存预后较差。大量免疫细胞和免疫检查点生物标志物的高表达，特别是程序性死亡配体-1（PD-L1）的高表达，已被证实显著影响疾病进展。我们分析了一组 SBA 患者的免疫细胞和免疫检查点生物标志物子集的表达情况，并评估了它们对无进展生存期（PFS）和总生存期（OS）的影响。
以组织微阵列（TMA）形式获得 25 例福尔马林固定、石蜡包埋（FFPE）组织的患者样本。使用针对 CD3、CD4、CD8、CD68、PD-L1、ICOS、IDO1 和 LAG3 的经过验证的抗体进行自动免疫组织化学（IHC）染色。将切片数字化扫描，并在开源图像分析软件 QuPath 中评估生物标志物密度和阳性百分比。使用 Kaplan-Meier 方法进行生存分析。
记录了不同的生物标志物表达。CD3、CD4 和 IDO1 的高表达与 PFS 显著相关（p = 0.043、0.020 和 0.018 分别）。ICOS 的高表达与 PFS（p = 0.040）和 OS（p = 0.041）均显著相关，而肿瘤细胞中 PD-L1 的高表达与 OS 显著相关（p = 0.033）。PD-L1 和 IDO1 的表达之间观察到高度相关性（皮尔逊相关系数= 1），随后发现肿瘤细胞中 IDO1 的高表达与 PFS（p = 0.006）和 OS（p = 0.034）显著相关。
高水平的免疫细胞和免疫检查点蛋白对 SBA 患者的生存有显著影响。这些数据可为 SBA 患者的免疫治疗管理提供参考。
