Turn tumor-related macrophages back into cancer fighters!

A form of cellular communication called hedgehog signaling is essential to mammalian embryonic development

Two years ago, Dr.

This signal transmission in the tumor microenvironment suggests that the use of existing, clinically approved hedgehog signaling inhibitors may reduce the tumor-promoting properties of tumor-associated M2 macrophages in the tumor microenvironment

"The charm of the hedgehog signaling target stems from the availability of several U.

"Therefore, inhibiting the hedgehog signaling pathway can bring the dual benefits of directly targeting tumor cells and reconfiguring the tumor immune microenvironment to an immune activated state

M1 and M2 macrophages have different metabolic circuits that contribute to their survival and different immune response functions

Using two mouse breast tumor models and treatment with the hedgehog inhibitor Vismodegib, Shevde and colleagues found that tumor-infiltrating macrophages changed significantly

This, in turn, has a downstream effect on the transcription factor STAT6, reducing its o-link-n-acetylglucosamine (O-GlcNAc) and modifying it to make it more active, resulting in a critical immunosuppressive state for M2 macrophages The expression of the genes Arg1 and Cd206 increased

However, when hedgehog inhibitors cause a decrease in o-glcnac modification of STAT6, the metabolism and bioenergy of macrophages shift from oxidative phosphorylation and fatty acid oxidation to glycolysis

Shevde said: "These hedgehog-suppressed macrophages are reminiscent of inflammatory M1 macrophages, and their phenotype is characterized by broken mitochondria

The Hedgehog signal includes the so-called Hedgehog protein, which binds to the cell and initiates the signal within the cell

DOI 10.

Hedgehog signaling regulates metabolism and polarization of mammary tumor2 associated macrophages