Department of Dermatology, University Medical Center of the Johannes Gutenberg University Mainz, 55131 Mainz, Germany.
Institute of Pathology, University Medical Center of the Johannes Gutenberg University Mainz, 55131 Mainz, Germany.
Cells. 2022 Nov 11;11(22):3570. doi: 10.3390/cells11223570.
Mycosis fungoides (MF) is the most common type of cutaneous T-cell lymphomas, characterized by mature, skin-tropic CD4+ T-helper cells. In order to study the immune tumor microenvironment in MF patients, we performed immunohistochemical stains on MF biopsies, digitized whole-slide tissue sections, and performed quantitative analysis of the different immune cell subsets to correlate tissue parameters with the clinical data of patients, such as progression-free survival or overall survival.
Overall, 35 patients who were treated between 2009 and 2019 and for whom one or more paraffin tissue blocks were available have been included in the present study (58 tissue specimens in total). Conventional immunohistochemistry stains for CD3, CD4, CD8, CD20 and CD30 were used for the analysis of the immune phenotype, and quantitative analysis was performed using QuPath as a quantitative digital pathology tool for bioimage analysis of whole slides.
Analysis of tissue parameters for prognostic significance revealed that patients with a stronger infiltration by CD8+ lymphocytes within the tumor cell compartment had a higher risk of disease progression ( = 0.031) and showed a shorter progress-free survival ( = 0.038). Furthermore, a significant association of the percentage of CD30+ cells (median: 7.8%) with the risk of disease progression ( = 0.023) and progression-free survival ( = 0.023) was found. In relation to the clinical features of our patient cohort, a higher risk of disease progression ( = 0.015) and a shorter progression-free survival ( = 0.032) for older patients (>61 years) were observed.
Our results demonstrated the prognostic relevance of large-cell transformation in mycosis fungoides and its strong association with the presence of CD30+ lymphocytes. Unlike previous reports, our study suggests an adverse prognostic role for CD8+ T cells in patients with mycosis fungoides. Moreover, our data indicate that the immune phenotype within the tumor microenvironment shows strong temporal heterogeneity and is altered in the course of tumor progression.
蕈样肉芽肿（MF）是最常见的皮肤 T 细胞淋巴瘤，其特征是成熟的、亲皮肤的 CD4+辅助性 T 细胞。为了研究 MF 患者的免疫肿瘤微环境，我们对 MF 活检组织进行了免疫组织化学染色，对全切片组织进行了数字化，并对不同免疫细胞亚群进行了定量分析，以将组织参数与患者的临床数据（如无进展生存期或总生存期）相关联。
本研究共纳入 2009 年至 2019 年间接受治疗且有一个或多个石蜡组织块的 35 例患者（共 58 个组织标本）。我们使用 CD3、CD4、CD8、CD20 和 CD30 的常规免疫组织化学染色来分析免疫表型，并使用 QuPath 作为定量数字病理学工具对全切片进行生物图像分析，进行定量分析。
对组织参数进行预后意义分析显示，肿瘤细胞区内 CD8+淋巴细胞浸润较强的患者疾病进展风险较高（ = 0.031），无进展生存期较短（ = 0.038）。此外，还发现 CD30+细胞的百分比（中位数：7.8%）与疾病进展风险（ = 0.023）和无进展生存期（ = 0.023）显著相关。与我们患者队列的临床特征相关，年龄较大（>61 岁）的患者疾病进展风险较高（ = 0.015），无进展生存期较短（ = 0.032）。
我们的结果表明蕈样肉芽肿的大细胞转化具有预后相关性，并且与 CD30+淋巴细胞的存在密切相关。与之前的报告不同，我们的研究表明 CD8+T 细胞在 MF 患者中具有不良的预后作用。此外，我们的数据表明肿瘤微环境中的免疫表型具有很强的时间异质性，并在肿瘤进展过程中发生改变。
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