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Single-cell sequencing reveals the landscape of the tumor microenvironment in a skeletal undifferentiated pleomorphic sarcoma patient
Skeletal undifferentiated pleomorphic sarcoma (SUPS) is an invasive pleomorphic soft tissue sarcoma with a high degree of malignancy and poor prognosis. It is prone to recur and metastasize. The tumor microenvironment (TME) and the pathophysiology of SUPS are barely described. Single-cell RNA sequen...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9709471/ https://www.ncbi.nlm.nih.gov/pubmed/36466840 http://dx.doi.org/10.3389/fimmu.2022.1019870 |
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author | Yuan, Liu-Liu Chen, Zhong Qin, Jian Qin, Cheng-Jiao Bian, Jing Dong, Rui-Fang Yuan, Tang-Bo Xu, Yi-Ting Kong, Ling-Yi Xia, Yuan-Zheng |
author_facet | Yuan, Liu-Liu Chen, Zhong Qin, Jian Qin, Cheng-Jiao Bian, Jing Dong, Rui-Fang Yuan, Tang-Bo Xu, Yi-Ting Kong, Ling-Yi Xia, Yuan-Zheng |
author_sort | Yuan, Liu-Liu |
collection | PubMed |
description | Skeletal undifferentiated pleomorphic sarcoma (SUPS) is an invasive pleomorphic soft tissue sarcoma with a high degree of malignancy and poor prognosis. It is prone to recur and metastasize. The tumor microenvironment (TME) and the pathophysiology of SUPS are barely described. Single-cell RNA sequencing (scRNA-seq) provides an opportunity to dissect the landscape of human diseases at an unprecedented resolution, particularly in diseases lacking animal models, such as SUPS. We performed scRNA-seq to analyze tumor tissues and paracancer tissues from a SUPS patient. We identified the cell types and the corresponding marker genes in this SUPS case. We further showed that CD8(+) exhausted T cells and Tregs highly expressed PDCD1, CTLA4 and TIGIT. Thus, PDCD1, CTLA4 and TIGIT were identified as potential targets in this case. We applied copy number karyotyping of aneuploid tumors (CopyKAT) to distinguish malignant cells from normal cells in fibroblasts. Our study identified eight malignant fibroblast subsets in SUPS with distinct gene expression profiles. C1-malignant Fibroblast and C6-malignant Fibroblast in the TME play crucial roles in tumor growth, angiogenesis, metastasis and immune response. Hence, targeting malignant fibroblasts could represent a potential strategy for this SUPS therapy. Intervention via tirelizumab enabled disease control, and immune checkpoint inhibitors (ICIs) of PD-1 may be considered as the first-line option in patients with SUPS. Taken together, scRNA-seq analyses provided a powerful basis for this SUPS treatment, improved our understanding of complex human diseases, and may afforded an alternative approach for personalized medicine in the future. |
format | Online Article Text |
id | pubmed-9709471 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-97094712022-12-01 Single-cell sequencing reveals the landscape of the tumor microenvironment in a skeletal undifferentiated pleomorphic sarcoma patient Yuan, Liu-Liu Chen, Zhong Qin, Jian Qin, Cheng-Jiao Bian, Jing Dong, Rui-Fang Yuan, Tang-Bo Xu, Yi-Ting Kong, Ling-Yi Xia, Yuan-Zheng Front Immunol Immunology Skeletal undifferentiated pleomorphic sarcoma (SUPS) is an invasive pleomorphic soft tissue sarcoma with a high degree of malignancy and poor prognosis. It is prone to recur and metastasize. The tumor microenvironment (TME) and the pathophysiology of SUPS are barely described. Single-cell RNA sequencing (scRNA-seq) provides an opportunity to dissect the landscape of human diseases at an unprecedented resolution, particularly in diseases lacking animal models, such as SUPS. We performed scRNA-seq to analyze tumor tissues and paracancer tissues from a SUPS patient. We identified the cell types and the corresponding marker genes in this SUPS case. We further showed that CD8(+) exhausted T cells and Tregs highly expressed PDCD1, CTLA4 and TIGIT. Thus, PDCD1, CTLA4 and TIGIT were identified as potential targets in this case. We applied copy number karyotyping of aneuploid tumors (CopyKAT) to distinguish malignant cells from normal cells in fibroblasts. Our study identified eight malignant fibroblast subsets in SUPS with distinct gene expression profiles. C1-malignant Fibroblast and C6-malignant Fibroblast in the TME play crucial roles in tumor growth, angiogenesis, metastasis and immune response. Hence, targeting malignant fibroblasts could represent a potential strategy for this SUPS therapy. Intervention via tirelizumab enabled disease control, and immune checkpoint inhibitors (ICIs) of PD-1 may be considered as the first-line option in patients with SUPS. Taken together, scRNA-seq analyses provided a powerful basis for this SUPS treatment, improved our understanding of complex human diseases, and may afforded an alternative approach for personalized medicine in the future. Frontiers Media S.A. 2022-11-16 /pmc/articles/PMC9709471/ /pubmed/36466840 http://dx.doi.org/10.3389/fimmu.2022.1019870 Text en Copyright © 2022 Yuan, Chen, Qin, Qin, Bian, Dong, Yuan, Xu, Kong and Xia https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Immunology Yuan, Liu-Liu Chen, Zhong Qin, Jian Qin, Cheng-Jiao Bian, Jing Dong, Rui-Fang Yuan, Tang-Bo Xu, Yi-Ting Kong, Ling-Yi Xia, Yuan-Zheng Single-cell sequencing reveals the landscape of the tumor microenvironment in a skeletal undifferentiated pleomorphic sarcoma patient |
title | Single-cell sequencing reveals the landscape of the tumor microenvironment in a skeletal undifferentiated pleomorphic sarcoma patient |
title_full | Single-cell sequencing reveals the landscape of the tumor microenvironment in a skeletal undifferentiated pleomorphic sarcoma patient |
title_fullStr | Single-cell sequencing reveals the landscape of the tumor microenvironment in a skeletal undifferentiated pleomorphic sarcoma patient |
title_full_unstemmed | Single-cell sequencing reveals the landscape of the tumor microenvironment in a skeletal undifferentiated pleomorphic sarcoma patient |
title_short | Single-cell sequencing reveals the landscape of the tumor microenvironment in a skeletal undifferentiated pleomorphic sarcoma patient |
title_sort | single-cell sequencing reveals the landscape of the tumor microenvironment in a skeletal undifferentiated pleomorphic sarcoma patient |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9709471/ https://www.ncbi.nlm.nih.gov/pubmed/36466840 http://dx.doi.org/10.3389/fimmu.2022.1019870 |
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