Kill two birds with one stone: Reprogramming tumor microenvironment with growth differentiation factor 11

A major driver of hepatocellular carcinoma (HCC)’s aggressiveness is its ability to hijack the immune system, specifically by recruiting immunosuppressive tumor-associated macrophages. These M2-type macrophages are coerced into promoting tumor growth and metastasis. This study by Escobedo-Calvario et al reveals that the protein growth differentiation factor 11 can effectively “re-educate” these pro-tumoral macrophages by reducing classic M2 markers, rewiring cellular metabolism, and boosting production of reactive oxygen species, which ultimately switch the macrophages from a pro-tumor state toward an anti-tumor state. When applied to HCC cells, growth differentiation factor 11 also reduced the cancer cells’ capacity to proliferate and migrate – key hallmarks of deadly metastasis. This two-pronged attack could represent a groundbreaking strategy to enhance current immunotherapies and control the aggressiveness of HCC, offering new hope for future treatments.