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...

Descripción completa

Detalles Bibliográficos
Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2022
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
_version_ 1784739500385107968
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
work_keys_str_mv AT tessarofernandohg singlecellrnaseqofasofttissuesarcomamodelrevealsthecriticalroleoftumorexpressedmifinshapingmacrophageheterogeneity
AT koemilyy singlecellrnaseqofasofttissuesarcomamodelrevealsthecriticalroleoftumorexpressedmifinshapingmacrophageheterogeneity
AT desimonemarco singlecellrnaseqofasofttissuesarcomamodelrevealsthecriticalroleoftumorexpressedmifinshapingmacrophageheterogeneity
AT pirasroberta singlecellrnaseqofasofttissuesarcomamodelrevealsthecriticalroleoftumorexpressedmifinshapingmacrophageheterogeneity
AT brozmarinat singlecellrnaseqofasofttissuesarcomamodelrevealsthecriticalroleoftumorexpressedmifinshapingmacrophageheterogeneity
AT goodridgehelens singlecellrnaseqofasofttissuesarcomamodelrevealsthecriticalroleoftumorexpressedmifinshapingmacrophageheterogeneity
AT balzerbonnie singlecellrnaseqofasofttissuesarcomamodelrevealsthecriticalroleoftumorexpressedmifinshapingmacrophageheterogeneity
AT shiaostephenl singlecellrnaseqofasofttissuesarcomamodelrevealsthecriticalroleoftumorexpressedmifinshapingmacrophageheterogeneity
AT guarneriojlenia singlecellrnaseqofasofttissuesarcomamodelrevealsthecriticalroleoftumorexpressedmifinshapingmacrophageheterogeneity