The cancer-associated fibroblasts interact with malignant T cells in mycosis fungoides and promote the disease progression
BackgroundCutaneous T-cell lymphoma (CTCL) is a heterogeneous group of T-cell lymphomas characterized with the presence of clonal malignant T cells. Mycosis fungoides (MF) is the most common type of CTCL. However, the pathogenesis of MF and the role of the tumor microenvironment (TME) remain unclear...
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Frontiers Media S.A.
2025-02-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1474564/full |
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| author | Yige Zhao Yong Li Yong Li Panpan Wang Mengyan Zhu Jiaqi Wang Bo Xie Chenyu Tang Yangyang Ma Shiwen Wang Sha Jin Jinhui Xu Zhao Li Xiaoyan Zhang Liuyu Li Xiuzu Song Ping Wang |
| author_facet | Yige Zhao Yong Li Yong Li Panpan Wang Mengyan Zhu Jiaqi Wang Bo Xie Chenyu Tang Yangyang Ma Shiwen Wang Sha Jin Jinhui Xu Zhao Li Xiaoyan Zhang Liuyu Li Xiuzu Song Ping Wang |
| author_sort | Yige Zhao |
| collection | DOAJ |
| description | BackgroundCutaneous T-cell lymphoma (CTCL) is a heterogeneous group of T-cell lymphomas characterized with the presence of clonal malignant T cells. Mycosis fungoides (MF) is the most common type of CTCL. However, the pathogenesis of MF and the role of the tumor microenvironment (TME) remain unclear.MethodsWe performed single-cell RNA sequencing on tumor and adjacent normal tissues and peripheral blood mononuclear cell (PBMC) from patients with advanced MF and healthy control (HC). We compared skin lesions in different stages within the same patient to overcome inter-individual variability.ResultsThe malignant clones displayed dual phenotypes characterized with tissue-resident memory T cells (TRMs) and central memory T cells (TCMs). We supposed that the tumor cells transformed from TRM-dominant phenotype to TCM-dominant phenotype during MF progressed from early-stage to advanced-stage. The cancer-associated fibroblasts (CAFs) showed active role in TME. The occurrence of inflammatory CAFs (iCAFs) may represent the advanced-stage MF. There may be mutual positive feedback of the crosstalk between tumor cells and CAFs during the MF development. Tumor cells promote CAF generation, and the CAFs, in turn, improve the invasiveness and metastasis of the malignant T cells through the IL-6/JAK2/STAT3/SOX4 or IL-6/HIF-1α/SOX4 pathway. SOX4 may be a critical regulatory gene of this positive feedback loop. Target SOX4 may disrupt the interactions between tumor cells and CAFs.ConclusionOur study revealed the origin and evolution trajectory of MF and uncovered the intercellular interactions between malignant T cells and CAFs, providing new insights into the novel treatment targets of MF. |
| format | Article |
| id | doaj-art-bc829f311aef41ec8513514e715283ef |
| institution | Kabale University |
| issn | 1664-3224 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj-art-bc829f311aef41ec8513514e715283ef2025-02-03T06:33:48ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-02-011510.3389/fimmu.2024.14745641474564The cancer-associated fibroblasts interact with malignant T cells in mycosis fungoides and promote the disease progressionYige Zhao0Yong Li1Yong Li2Panpan Wang3Mengyan Zhu4Jiaqi Wang5Bo Xie6Chenyu Tang7Yangyang Ma8Shiwen Wang9Sha Jin10Jinhui Xu11Zhao Li12Xiaoyan Zhang13Liuyu Li14Xiuzu Song15Ping Wang16Department of Dermatology, Hangzhou Third People's Hospital, Hangzhou Third Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou, ChinaDepartment of Dermatology, Hangzhou Third People's Hospital, Hangzhou Third Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou, ChinaResearch Center, Shanghai Yeslab Biotechnology, Shanghai, ChinaDepartment of Dermatology, Shaoxing People's Hospital, Shaoxing, ChinaDepartment of Dermatology, Hangzhou Third People's Hospital, Hangzhou Third Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou, ChinaDepartment of Dermatology, Hangzhou Third People's Hospital, Hangzhou Third Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou, ChinaDepartment of Dermatology, Hangzhou Third People's Hospital, Hangzhou Third Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou, ChinaDepartment of Dermatology, Hangzhou Third People's Hospital, Zhejiang Chinese Medical University, Hangzhou, ChinaDepartment of Dermatology, Hangzhou Third People's Hospital, Hangzhou Third Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou, ChinaDepartment of Dermatology, Hangzhou Third People's Hospital, Zhejiang Chinese Medical University, Hangzhou, ChinaDepartment of Dermatology, Hangzhou Third People's Hospital, Zhejiang Chinese Medical University, Hangzhou, ChinaDepartment of Dermatology, Hangzhou Third People's Hospital, Hangzhou Third Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou, ChinaDepartment of Dermatology, Hangzhou Third People's Hospital, Hangzhou Third Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou, ChinaDepartment of Dermatology, Hangzhou Third People's Hospital, Hangzhou Third Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou, ChinaDepartment of Dermatology, Hangzhou Third People's Hospital, Hangzhou Third Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou, ChinaDepartment of Dermatology, Hangzhou Third People's Hospital, Hangzhou Third Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou, ChinaDepartment of Dermatology, Hangzhou Third People's Hospital, Hangzhou Third Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou, ChinaBackgroundCutaneous T-cell lymphoma (CTCL) is a heterogeneous group of T-cell lymphomas characterized with the presence of clonal malignant T cells. Mycosis fungoides (MF) is the most common type of CTCL. However, the pathogenesis of MF and the role of the tumor microenvironment (TME) remain unclear.MethodsWe performed single-cell RNA sequencing on tumor and adjacent normal tissues and peripheral blood mononuclear cell (PBMC) from patients with advanced MF and healthy control (HC). We compared skin lesions in different stages within the same patient to overcome inter-individual variability.ResultsThe malignant clones displayed dual phenotypes characterized with tissue-resident memory T cells (TRMs) and central memory T cells (TCMs). We supposed that the tumor cells transformed from TRM-dominant phenotype to TCM-dominant phenotype during MF progressed from early-stage to advanced-stage. The cancer-associated fibroblasts (CAFs) showed active role in TME. The occurrence of inflammatory CAFs (iCAFs) may represent the advanced-stage MF. There may be mutual positive feedback of the crosstalk between tumor cells and CAFs during the MF development. Tumor cells promote CAF generation, and the CAFs, in turn, improve the invasiveness and metastasis of the malignant T cells through the IL-6/JAK2/STAT3/SOX4 or IL-6/HIF-1α/SOX4 pathway. SOX4 may be a critical regulatory gene of this positive feedback loop. Target SOX4 may disrupt the interactions between tumor cells and CAFs.ConclusionOur study revealed the origin and evolution trajectory of MF and uncovered the intercellular interactions between malignant T cells and CAFs, providing new insights into the novel treatment targets of MF.https://www.frontiersin.org/articles/10.3389/fimmu.2024.1474564/fullmycosis fungoides (MF)cutaneous T cell lymphoma (CTCL)tissue resident memory T cell (TRM)cancer-associated fibroblast (CAF)tumor microenvironmentSOX4 |
| spellingShingle | Yige Zhao Yong Li Yong Li Panpan Wang Mengyan Zhu Jiaqi Wang Bo Xie Chenyu Tang Yangyang Ma Shiwen Wang Sha Jin Jinhui Xu Zhao Li Xiaoyan Zhang Liuyu Li Xiuzu Song Ping Wang The cancer-associated fibroblasts interact with malignant T cells in mycosis fungoides and promote the disease progression Frontiers in Immunology mycosis fungoides (MF) cutaneous T cell lymphoma (CTCL) tissue resident memory T cell (TRM) cancer-associated fibroblast (CAF) tumor microenvironment SOX4 |
| title | The cancer-associated fibroblasts interact with malignant T cells in mycosis fungoides and promote the disease progression |
| title_full | The cancer-associated fibroblasts interact with malignant T cells in mycosis fungoides and promote the disease progression |
| title_fullStr | The cancer-associated fibroblasts interact with malignant T cells in mycosis fungoides and promote the disease progression |
| title_full_unstemmed | The cancer-associated fibroblasts interact with malignant T cells in mycosis fungoides and promote the disease progression |
| title_short | The cancer-associated fibroblasts interact with malignant T cells in mycosis fungoides and promote the disease progression |
| title_sort | cancer associated fibroblasts interact with malignant t cells in mycosis fungoides and promote the disease progression |
| topic | mycosis fungoides (MF) cutaneous T cell lymphoma (CTCL) tissue resident memory T cell (TRM) cancer-associated fibroblast (CAF) tumor microenvironment SOX4 |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1474564/full |
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