The Role of the Immune Phenotype in Tumor Progression and Prognosis of Patients with Mycosis Fungoides: A Quantitative Immunohistology Whole Slide Approach

<span style="text-decoration: underline;">Background and objectives:</span> 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...

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Main Authors: Natallia Aulasevich, Maximilian Haist, Sebastian Försch, Beate Weidenthaler-Barth, Volker Mailänder
Format: Article
Language:English
Published: MDPI AG 2022-11-01
Series:Cells
Subjects:
Online Access:https://www.mdpi.com/2073-4409/11/22/3570
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author Natallia Aulasevich
Maximilian Haist
Sebastian Försch
Beate Weidenthaler-Barth
Volker Mailänder
author_facet Natallia Aulasevich
Maximilian Haist
Sebastian Försch
Beate Weidenthaler-Barth
Volker Mailänder
author_sort Natallia Aulasevich
collection DOAJ
description <span style="text-decoration: underline;">Background and objectives:</span> 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. <span style="text-decoration: underline;">Patients and methods</span>: 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. <span style="text-decoration: underline;">Results</span>: 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 (<i>p</i> = 0.031) and showed a shorter progress-free survival (<i>p</i> = 0.038). Furthermore, a significant association of the percentage of CD30+ cells (median: 7.8%) with the risk of disease progression (<i>p</i> = 0.023) and progression-free survival (<i>p</i> = 0.023) was found. In relation to the clinical features of our patient cohort, a higher risk of disease progression (<i>p</i> = 0.015) and a shorter progression-free survival (<i>p</i> = 0.032) for older patients (>61 years) were observed. <span style="text-decoration: underline;">Conclusions</span>: 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.
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spelling doaj.art-1cda16a7add24b6caf7ba42a5736cbfb2023-11-24T07:57:34ZengMDPI AGCells2073-44092022-11-011122357010.3390/cells11223570The Role of the Immune Phenotype in Tumor Progression and Prognosis of Patients with Mycosis Fungoides: A Quantitative Immunohistology Whole Slide ApproachNatallia Aulasevich0Maximilian Haist1Sebastian Försch2Beate Weidenthaler-Barth3Volker Mailänder4Department of Dermatology, University Medical Center of the Johannes Gutenberg University Mainz, 55131 Mainz, GermanyDepartment of Dermatology, University Medical Center of the Johannes Gutenberg University Mainz, 55131 Mainz, GermanyInstitute of Pathology, University Medical Center of the Johannes Gutenberg University Mainz, 55131 Mainz, GermanyDepartment of Dermatology, University Medical Center of the Johannes Gutenberg University Mainz, 55131 Mainz, GermanyDepartment of Dermatology, University Medical Center of the Johannes Gutenberg University Mainz, 55131 Mainz, Germany<span style="text-decoration: underline;">Background and objectives:</span> 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. <span style="text-decoration: underline;">Patients and methods</span>: 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. <span style="text-decoration: underline;">Results</span>: 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 (<i>p</i> = 0.031) and showed a shorter progress-free survival (<i>p</i> = 0.038). Furthermore, a significant association of the percentage of CD30+ cells (median: 7.8%) with the risk of disease progression (<i>p</i> = 0.023) and progression-free survival (<i>p</i> = 0.023) was found. In relation to the clinical features of our patient cohort, a higher risk of disease progression (<i>p</i> = 0.015) and a shorter progression-free survival (<i>p</i> = 0.032) for older patients (>61 years) were observed. <span style="text-decoration: underline;">Conclusions</span>: 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.https://www.mdpi.com/2073-4409/11/22/3570mycosis fungoidesimmune phenotypeimmunohistochemistrytumor microenvironmentCD30prognosis
spellingShingle Natallia Aulasevich
Maximilian Haist
Sebastian Försch
Beate Weidenthaler-Barth
Volker Mailänder
The Role of the Immune Phenotype in Tumor Progression and Prognosis of Patients with Mycosis Fungoides: A Quantitative Immunohistology Whole Slide Approach
Cells
mycosis fungoides
immune phenotype
immunohistochemistry
tumor microenvironment
CD30
prognosis
title The Role of the Immune Phenotype in Tumor Progression and Prognosis of Patients with Mycosis Fungoides: A Quantitative Immunohistology Whole Slide Approach
title_full The Role of the Immune Phenotype in Tumor Progression and Prognosis of Patients with Mycosis Fungoides: A Quantitative Immunohistology Whole Slide Approach
title_fullStr The Role of the Immune Phenotype in Tumor Progression and Prognosis of Patients with Mycosis Fungoides: A Quantitative Immunohistology Whole Slide Approach
title_full_unstemmed The Role of the Immune Phenotype in Tumor Progression and Prognosis of Patients with Mycosis Fungoides: A Quantitative Immunohistology Whole Slide Approach
title_short The Role of the Immune Phenotype in Tumor Progression and Prognosis of Patients with Mycosis Fungoides: A Quantitative Immunohistology Whole Slide Approach
title_sort role of the immune phenotype in tumor progression and prognosis of patients with mycosis fungoides a quantitative immunohistology whole slide approach
topic mycosis fungoides
immune phenotype
immunohistochemistry
tumor microenvironment
CD30
prognosis
url https://www.mdpi.com/2073-4409/11/22/3570
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