Single-cell RNA-seq of a Soft-tissue Sarcoma Model Reveals the Critical Role of Tumor-expressed MIF in Shaping Macrophage Heterogeneity

Overview

Journal Cell Rep

Publisher Cell Press

Specialties Biology
Cell Biology
Molecular Biology

Date 2022 Jun 22

PMID 35732118

Authors

Fernando H G Tessaro

Emily Y Ko

Marco De Simone

Roberta Piras

Marina T Broz

Helen S Goodridge

Bonnie Balzer

Stephen L Shiao

Jlenia Guarnerio

Affiliations

Soon will be listed here.

Abstract

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.

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