Journal
CELL REPORTS
Volume 39, Issue 12, Pages -Publisher
CELL PRESS
DOI: 10.1016/j.celrep.2022.110977
Keywords
-
Categories
Funding
- NIH/NCI [K99/R00 CA212200, R01 CA258265]
- Sarcoma Foundation of America [2019 SFA 15-19]
- Cedars-Sinai Cancer Center
Ask authors/readers for more resources
This study characterized the immune composition of an undifferentiated pleiomorphic sarcoma mouse model using single-cell RNA sequencing. The researchers found that macrophages in the sarcoma mass exhibit distinct activation states. Sarcoma cells use MIF to interact with macrophages and switch their activation state, promoting tumor growth. Blocking MIF expression in sarcoma cells reduces tumor growth.
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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available