Pathology Laboratory, Department of Pathology and Laboratory Diagnostics, Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw, Poland; Department of Diagnostic Hematology, Institute of Hematology and Transfusion Medicine, Warsaw, Poland.
Nalecz Institute of Biocybernetics and Biomedical Engineering, Polish Academy of Sciences, Poland; Department of Computational Oncology, Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw, Poland.
Pathol Res Pract. 2020 Oct;216(10):153096. doi: 10.1016/j.prp.2020.153096. Epub 2020 Jun 29.
Follicular lymphoma (FL) is a well-studied microenvironment-dependent hematological malignancy, but the crosstalk between various involved cell subtypes is still not fully understood. Recent promising results of immunotherapy in recurrent FL warrant the need for an in-depth analysis of the expression and role of immune system-related proteins in the FL microenvironment. Seventy-one patients with FL and available diagnostic paraffin blocks were enrolled in the retrospective analysis. Histopathological diagnoses were revised according to the World Health Organization recommendations. Patients were either observed (watch and wait/W&W group) or immediately treated with chemo(immuno)therapy regimens according to their clinical status. Immunohistochemical assessment of PD1, PDL1, CD4, CD8, CD163, CD68-KP1, CD68-PGM1 was performed. The scoring methods included both semi-quantitative estimation of positive cells and architectural pattern distribution. The differences between PD1 staining distribution and intensity were classified as intra/perifollicular vs. interfollicular/diffuse cells and presented bright vs. dim immunoreactivity, respectively. No statistically significant differences in the density distribution of the immunohistochemical stainings were found between W&W and chemo(immuno)therapy groups. Interfollicular/diffuse pattern of PD1 expression had significantly decreased progression-free survival when analyzing the whole cohort and patients on chemo(immuno)therapy (p = 0.014 and p = 0.07, respectively). The high dependence was not significant in the W&W group. PD1 positivity of cells did not correlate with CD4 or CD8 immunophenotype. Morphologically FL neoplastic cells were entirely PDL1 negative, but granular and membranous staining was detected in the FL microenvironment. In line with previous studies, PD1/PDL1 expression was predominantly localized in the FL microenvironment, indicating that FL cells might not be the direct target for anti-PDL1 therapy. However, we show that the localization of PD1 expression could be a viable progression-free survival biomarker for FL.
滤泡性淋巴瘤（FL）是一种研究较为透彻的依赖于微环境的血液恶性肿瘤，但各种相关细胞亚型之间的相互作用仍不完全清楚。最近免疫疗法在复发性 FL 中的可喜结果证明需要深入分析 FL 微环境中免疫系统相关蛋白的表达和作用。本回顾性分析纳入了 71 例 FL 患者和可用的诊断石蜡块。根据世界卫生组织的建议修订了组织病理学诊断。根据患者的临床状况，要么观察（观察等待/W&W 组），要么立即用化疗（免疫）治疗方案治疗。进行了 PD1、PDL1、CD4、CD8、CD163、CD68-KP1、CD68-PGM1 的免疫组织化学评估。评分方法包括阳性细胞的半定量估计和结构分布。PD1 染色分布和强度的差异分别分为滤泡内/滤泡间与弥漫细胞，并分别呈现明亮与暗淡的免疫反应性。在 W&W 和化疗（免疫）治疗组之间，免疫组化染色的密度分布没有统计学差异。当分析整个队列和接受化疗（免疫）治疗的患者时，PD1 表达的滤泡间/弥漫性模式与无进展生存期显著相关（p=0.014 和 p=0.07）。在 W&W 组，高依赖性不显著。PD1 阳性细胞与 CD4 或 CD8 免疫表型无关。形态上，FL 肿瘤细胞完全 PD-L1 阴性，但在 FL 微环境中检测到颗粒状和膜状染色。与先前的研究一致，PD1/PDL1 表达主要定位于 FL 微环境，表明 FL 细胞可能不是抗 PD-L1 治疗的直接靶点。然而，我们表明 PD1 表达的定位可能是 FL 无进展生存期的一个可行的生物标志物。
