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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2025-01-01
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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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institution | Kabale University |
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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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