Single-cell RNA-seq of a soft-tissue sarcoma model reveals the critical role of tumor-expressed MIF in shaping macrophage heterogeneity
The standard of care is unsuccessful to treat recurrent and aggressive soft-tissue sarcomas. Interventions aimed at targeting components of the tumor microenvironment have shown promise for many solid tumors yet have been only marginally tested for sarcoma, partly because knowledge of the sarcoma mi...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9249098/ https://www.ncbi.nlm.nih.gov/pubmed/35732118 http://dx.doi.org/10.1016/j.celrep.2022.110977 |
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author | Tessaro, Fernando H.G. Ko, Emily Y. De Simone, Marco Piras, Roberta Broz, Marina T. Goodridge, Helen S. Balzer, Bonnie Shiao, Stephen L. Guarnerio, Jlenia |
author_facet | Tessaro, Fernando H.G. Ko, Emily Y. De Simone, Marco Piras, Roberta Broz, Marina T. Goodridge, Helen S. Balzer, Bonnie Shiao, Stephen L. Guarnerio, Jlenia |
author_sort | Tessaro, Fernando H.G. |
collection | PubMed |
description | The standard of care is unsuccessful to treat recurrent and aggressive soft-tissue sarcomas. Interventions aimed at targeting components of the tumor microenvironment have shown promise for many solid tumors yet have been only marginally tested for sarcoma, partly because knowledge of the sarcoma microenvironment composition is limited. We employ single-cell RNA sequencing to characterize the immune composition of an undifferentiated pleiomorphic sarcoma mouse model, showing that macrophages in the sarcoma mass exhibit distinct activation states. Sarcoma cells use the pleiotropic cytokine macrophage migration inhibitory factor (MIF) to interact with macrophages expressing the CD74 receptor to switch macrophages’ activation state and pro-tumorigenic potential. Blocking the expression of MIF in sarcoma cells favors the accumulation of macrophages with inflammatory and antigen-presenting profiles, hence reducing tumor growth. These data may pave the way for testing new therapies aimed at re-shaping the sarcoma microenvironment, in combination with the standard of care. |
format | Online Article Text |
id | pubmed-9249098 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
record_format | MEDLINE/PubMed |
spelling | pubmed-92490982022-07-01 Single-cell RNA-seq of a soft-tissue sarcoma model reveals the critical role of tumor-expressed MIF in shaping macrophage heterogeneity Tessaro, Fernando H.G. Ko, Emily Y. De Simone, Marco Piras, Roberta Broz, Marina T. Goodridge, Helen S. Balzer, Bonnie Shiao, Stephen L. Guarnerio, Jlenia Cell Rep Article The standard of care is unsuccessful to treat recurrent and aggressive soft-tissue sarcomas. Interventions aimed at targeting components of the tumor microenvironment have shown promise for many solid tumors yet have been only marginally tested for sarcoma, partly because knowledge of the sarcoma microenvironment composition is limited. We employ single-cell RNA sequencing to characterize the immune composition of an undifferentiated pleiomorphic sarcoma mouse model, showing that macrophages in the sarcoma mass exhibit distinct activation states. Sarcoma cells use the pleiotropic cytokine macrophage migration inhibitory factor (MIF) to interact with macrophages expressing the CD74 receptor to switch macrophages’ activation state and pro-tumorigenic potential. Blocking the expression of MIF in sarcoma cells favors the accumulation of macrophages with inflammatory and antigen-presenting profiles, hence reducing tumor growth. These data may pave the way for testing new therapies aimed at re-shaping the sarcoma microenvironment, in combination with the standard of care. 2022-06-21 /pmc/articles/PMC9249098/ /pubmed/35732118 http://dx.doi.org/10.1016/j.celrep.2022.110977 Text en https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) ). |
spellingShingle | Article Tessaro, Fernando H.G. Ko, Emily Y. De Simone, Marco Piras, Roberta Broz, Marina T. Goodridge, Helen S. Balzer, Bonnie Shiao, Stephen L. Guarnerio, Jlenia Single-cell RNA-seq of a soft-tissue sarcoma model reveals the critical role of tumor-expressed MIF in shaping macrophage heterogeneity |
title | Single-cell RNA-seq of a soft-tissue sarcoma model reveals the critical role of tumor-expressed MIF in shaping macrophage heterogeneity |
title_full | Single-cell RNA-seq of a soft-tissue sarcoma model reveals the critical role of tumor-expressed MIF in shaping macrophage heterogeneity |
title_fullStr | Single-cell RNA-seq of a soft-tissue sarcoma model reveals the critical role of tumor-expressed MIF in shaping macrophage heterogeneity |
title_full_unstemmed | Single-cell RNA-seq of a soft-tissue sarcoma model reveals the critical role of tumor-expressed MIF in shaping macrophage heterogeneity |
title_short | Single-cell RNA-seq of a soft-tissue sarcoma model reveals the critical role of tumor-expressed MIF in shaping macrophage heterogeneity |
title_sort | single-cell rna-seq of a soft-tissue sarcoma model reveals the critical role of tumor-expressed mif in shaping macrophage heterogeneity |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9249098/ https://www.ncbi.nlm.nih.gov/pubmed/35732118 http://dx.doi.org/10.1016/j.celrep.2022.110977 |
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