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Single-cell RNA-seq analysis of a soft-tissue sarcoma model reveals the critical role of tumor expressed MIF in shaping macrophage heterogeneity.

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus

PROVIDER: GSE201619 | GEO | 2022/07/06

REPOSITORIES: GEO

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Single-cell RNA-seq of a soft-tissue sarcoma model reveals the critical role of tumor-expressed MIF in shaping macrophage heterogeneity.

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Single-cell RNA-seq analysis of a soft-tissue sarcoma model reveals the critical role of tumor expressed MIF in shaping macrophage heterogeneity. [CITE-Seq]

Project 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 employed 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 used 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 favored 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.

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Project description:Single-cell RNA-seq analysis of a soft-tissue sarcoma model reveals the critical role of tumor expressed MIF in shaping macrophage heterogeneity.

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