Researchers uncover dual role of B7-H3 in prostate tumor immune suppression

Researchers at The University of Texas MD Anderson Cancer Center have discovered that prostate tumors employ a dual strategy to evade the immune system by manipulating the tumor microenvironment. Led by Dr. Di Zhao and Dr. Nicholas Navin, the study reveals that B7-H3, an immune checkpoint protein, not only halts immune responses but also reshapes surrounding cells to bolster the tumor's resistance to treatment.

In preclinical models of castration-resistant prostate cancer, B7-H3 directly interacts with a subset of immune cells called monocytic MDSCs, activating a signaling pathway that pushes these cells into a senescent state. This transition causes senescent cells to discharge inflammatory molecules that alter the tumor microenvironment and recruit additional suppressive immune cells.

However, in response to B7-H3 inhibition, MDSCs generate elevated levels of a protein that stimulates fibroblasts to strengthen the tumor's structural barrier.

The study demonstrates that combining B7-H3-targeted therapy with MEK inhibition using trametinib, an FDA-approved inhibitor, effectively curtails tumor growth and extends survival more efficiently than either treatment independently. The combination reduces suppressive MDSCs, limits fibroblast-related tissue remodeling, and enhances T cell infiltration into tumors.

While these findings are preclinical and require further validation, they offer compelling evidence supporting the potential of this dual therapy approach for guiding future clinical trials in advanced prostate cancer patients.