The Progression of Mycosis Fungoides During Treatment with Mogamulizumab: A BIO-MUSE Case Study of the Tumor and Immune Response in Peripheral Blood and Tissue

<b>Background/objectives:</b> Mycosis fungoides (MF) is a rare malignancy, with an indolent course in the early stages of the disease. However, due to major molecular and clinical heterogeneity, patients at an advanced stage of the disease have variable responses to treatment and conside...

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Main Authors: Angelica Johansson, Eirini Kalliara, Emma Belfrage, Teodor Alling, Paul Theodor Pyl, Anna Sandström Gerdtsson, Urban Gullberg, Anna Porwit, Kristina Drott, Sara Ek
Format: Article
Language:English
Published: MDPI AG 2025-01-01
Series:Biomedicines
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Online Access:https://www.mdpi.com/2227-9059/13/1/186
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author Angelica Johansson
Eirini Kalliara
Emma Belfrage
Teodor Alling
Paul Theodor Pyl
Anna Sandström Gerdtsson
Urban Gullberg
Anna Porwit
Kristina Drott
Sara Ek
author_facet Angelica Johansson
Eirini Kalliara
Emma Belfrage
Teodor Alling
Paul Theodor Pyl
Anna Sandström Gerdtsson
Urban Gullberg
Anna Porwit
Kristina Drott
Sara Ek
author_sort Angelica Johansson
collection DOAJ
description <b>Background/objectives:</b> Mycosis fungoides (MF) is a rare malignancy, with an indolent course in the early stages of the disease. However, due to major molecular and clinical heterogeneity, patients at an advanced stage of the disease have variable responses to treatment and considerably reduced life expectancy. Today, there is a lack of specific markers for the progression from early to advanced stages of the disease. To address these challenges, the non-interventional BIO-MUSE trial was initiated. Here, we report on a case study involving one patient, where combined omics analysis of tissue and blood was used to reveal the unique molecular features associated with the progression of the disease. <b>Methods:</b> We applied 10× genomics-based single-cell RNA sequencing to CD3+ peripheral T-cells, combined with T-cell receptor sequencing, to samples collected at multiple timepoints during the progression of the disease. In addition, GeoMx-based digital spatial profiling of T-helper (CD3+/CD8−), T-cytotoxic (CD3+/CD8+), and CD163+ cells was performed on skin biopsies. <b>Results.</b> The results pinpoint targets, such as transforming growth factor β1, as some of the mechanisms underlying disease progression, which may have the potential to improve patient prognostication and the development of precision medicine efforts. <b>Conclusions:</b> We propose that in patients with MF, the evolution of the malignant clone and the associated immune response need to be studied jointly to define relevant strategies for intervention.
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spelling doaj-art-a47c509e07b84f62998420b223a040012025-01-24T13:24:19ZengMDPI AGBiomedicines2227-90592025-01-0113118610.3390/biomedicines13010186The Progression of Mycosis Fungoides During Treatment with Mogamulizumab: A BIO-MUSE Case Study of the Tumor and Immune Response in Peripheral Blood and TissueAngelica Johansson0Eirini Kalliara1Emma Belfrage2Teodor Alling3Paul Theodor Pyl4Anna Sandström Gerdtsson5Urban Gullberg6Anna Porwit7Kristina Drott8Sara Ek9Department of Immunotechnology, Faculty of Engineering (LTH), Lund University, 223 63 Lund, SwedenDepartment of Immunotechnology, Faculty of Engineering (LTH), Lund University, 223 63 Lund, SwedenDepartment of Dermatology and Venereology, Skane University Hospital (SUS), 205 02 Lund, SwedenDepartment of Immunotechnology, Faculty of Engineering (LTH), Lund University, 223 63 Lund, SwedenDepartment of Laboratory Medicine, National Bioinformatics Infrastructure Sweden, Science for Life Laboratory, Lund University, 221 00 Lund, SwedenDepartment of Immunotechnology, Faculty of Engineering (LTH), Lund University, 223 63 Lund, SwedenDepartment of Laboratory Medicine, Lund University, 221 00 Lund, SwedenDivision of Pathology, Department of Clinical Sciences, 221 00 Lund, SwedenDivision of Medical Oncology, Department of Clinical Sciences, 221 00 Lund, SwedenDepartment of Immunotechnology, Faculty of Engineering (LTH), Lund University, 223 63 Lund, Sweden<b>Background/objectives:</b> Mycosis fungoides (MF) is a rare malignancy, with an indolent course in the early stages of the disease. However, due to major molecular and clinical heterogeneity, patients at an advanced stage of the disease have variable responses to treatment and considerably reduced life expectancy. Today, there is a lack of specific markers for the progression from early to advanced stages of the disease. To address these challenges, the non-interventional BIO-MUSE trial was initiated. Here, we report on a case study involving one patient, where combined omics analysis of tissue and blood was used to reveal the unique molecular features associated with the progression of the disease. <b>Methods:</b> We applied 10× genomics-based single-cell RNA sequencing to CD3+ peripheral T-cells, combined with T-cell receptor sequencing, to samples collected at multiple timepoints during the progression of the disease. In addition, GeoMx-based digital spatial profiling of T-helper (CD3+/CD8−), T-cytotoxic (CD3+/CD8+), and CD163+ cells was performed on skin biopsies. <b>Results.</b> The results pinpoint targets, such as transforming growth factor β1, as some of the mechanisms underlying disease progression, which may have the potential to improve patient prognostication and the development of precision medicine efforts. <b>Conclusions:</b> We propose that in patients with MF, the evolution of the malignant clone and the associated immune response need to be studied jointly to define relevant strategies for intervention.https://www.mdpi.com/2227-9059/13/1/186biomarker discoverycutaneous T-cell lymphomamycosis fungoidespatient prognosticationpersonalized medicinespatially resolved transcriptomics
spellingShingle Angelica Johansson
Eirini Kalliara
Emma Belfrage
Teodor Alling
Paul Theodor Pyl
Anna Sandström Gerdtsson
Urban Gullberg
Anna Porwit
Kristina Drott
Sara Ek
The Progression of Mycosis Fungoides During Treatment with Mogamulizumab: A BIO-MUSE Case Study of the Tumor and Immune Response in Peripheral Blood and Tissue
Biomedicines
biomarker discovery
cutaneous T-cell lymphoma
mycosis fungoides
patient prognostication
personalized medicine
spatially resolved transcriptomics
title The Progression of Mycosis Fungoides During Treatment with Mogamulizumab: A BIO-MUSE Case Study of the Tumor and Immune Response in Peripheral Blood and Tissue
title_full The Progression of Mycosis Fungoides During Treatment with Mogamulizumab: A BIO-MUSE Case Study of the Tumor and Immune Response in Peripheral Blood and Tissue
title_fullStr The Progression of Mycosis Fungoides During Treatment with Mogamulizumab: A BIO-MUSE Case Study of the Tumor and Immune Response in Peripheral Blood and Tissue
title_full_unstemmed The Progression of Mycosis Fungoides During Treatment with Mogamulizumab: A BIO-MUSE Case Study of the Tumor and Immune Response in Peripheral Blood and Tissue
title_short The Progression of Mycosis Fungoides During Treatment with Mogamulizumab: A BIO-MUSE Case Study of the Tumor and Immune Response in Peripheral Blood and Tissue
title_sort progression of mycosis fungoides during treatment with mogamulizumab a bio muse case study of the tumor and immune response in peripheral blood and tissue
topic biomarker discovery
cutaneous T-cell lymphoma
mycosis fungoides
patient prognostication
personalized medicine
spatially resolved transcriptomics
url https://www.mdpi.com/2227-9059/13/1/186
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