Department of Pathology and Immunology, Washington University School of Medicine, St Louis, MO, USA.
Department of Pathology and Immunology, Washington University School of Medicine, St Louis, MO, USA.
Pathology. 2024 Oct;56(6):814-825. doi: 10.1016/j.pathol.2024.03.005. Epub 2024 May 21.
Wilms tumour (WT) is the most common renal tumour in children, and studies of immune checkpoint inhibitors (ICIs) treatment and markers are limited in number. In this study we investigated the ICIs' related immune landscape by examining the expression of PD-L1, PD-1, CD8 and DNA mismatch repair (MMR) proteins by immunohistochemistry (IHC), tumour mutation burden (TMB), and correlations with histology and clinical outcome. Positive PD-L1 (SP263) expression was defined as modified combined positive score (CPS) ≥1. A total of 59 WTs (from 2000 to 2017), including eight (14.0%) with anaplasia, from 46 patients were analysed (45 primary and 14 metastatic). Thirteen WTs (13/59, 22%) were positive for PD-L1 (8 primary, 5 metastatic; CPS 1.11-3.42). Positive PD-L1 expression was associated with diffuse anaplasia (p<0.05) and significantly shorter progression-free survival (p<0.05) among WTs with favourable histology (n=39). CD8+ lymphocytes were present in all analysed WTs. A subset of CD8+ cells co-expressed PD-1, which was associated with favourable histology and treatment. MMR IHC stains identified two (2/18, 11%) WTs with isolated PMS2 loss. All six WTs analysed for TMB showed low mutation burden. We found CD8+ lymphocytes in all analysed WTs and identified a fraction of WT (17.8% of primary and 35.8% of metastatic) with positive PD-L1 CPS, suggesting potential response to ICIs in some patients.
Wilms 瘤（WT）是儿童中最常见的肾肿瘤，关于免疫检查点抑制剂（ICI）治疗和标志物的研究数量有限。在这项研究中，我们通过免疫组织化学（IHC）检查 PD-L1、PD-1、CD8 和错配修复（MMR）蛋白的表达、肿瘤突变负担（TMB），并与组织学和临床结果相关联，来研究 ICI 相关的免疫图谱。阳性 PD-L1（SP263）表达被定义为改良联合阳性评分（CPS）≥1。共分析了 59 例 WT（2000 年至 2017 年），包括 8 例（14.0%）间变性，来自 46 例患者（45 例原发和 14 例转移）。13 例 WT（13/59，22%）PD-L1 阳性（8 例原发，5 例转移；CPS 为 1.11-3.42）。在具有良好组织学特征的 WT 中（n=39），阳性 PD-L1 表达与弥漫性间变性（p<0.05）和无进展生存率显著缩短（p<0.05）相关。所有分析的 WT 中均存在 CD8+淋巴细胞。一部分 CD8+细胞共表达 PD-1，与良好的组织学和治疗相关。MMR IHC 染色鉴定出 2 例（2/18，11%）WT 存在孤立的 PMS2 缺失。所有 6 例分析的 TMB 显示低突变负担。我们在所有分析的 WT 中均发现 CD8+淋巴细胞，并鉴定出一部分 WT（17.8%的原发和 35.8%的转移）PD-L1 CPS 阳性，提示某些患者可能对 ICI 有反应。
