Transforming growth factor β signaling in myeloid cells is required for tumor metastasis

Menée à l'aide de modèles murins, cette étude met en évidence le rôle joué par la signalisation TGFβ dans les cellules myéloïdes pour favoriser le processus métastatique

Résumé en anglais

TGFβ is over expressed in advanced human cancers. It correlates with metastasis and poor prognosis. However, TGFβ functions as both a tumor suppressor and a tumor promoter. Here we report for the first time that genetic deletion of Tgfbr2 specifically in myeloid cells (Tgfbr2MyeKO) significantly inhibited tumor metastasis. Reconstitution of tumor-bearing mice with Tgfbr2MyeKO bone marrow recapitulates the inhibited metastasis phenotype. This effect is mediated through decreased production of type 2 cytokines, TGFβ1, arginase 1 and iNOS, which promoted IFN-γ production and improved systemic immunity. Depletion of CD8 T cells diminished metastasis defect in the Tgfbr2MyeKO mice. Consistent with animal studies, myeloid cells from advanced stage cancer patients demonstrated an increased TGFβ receptor II expression. Our studies demonstrate that myeloid-specific TGFβ signaling is an essential component of the metastasis-promoting puzzle of TGFβ. This is in contrast to the previously reported tumor-suppressing phenotypes in fibroblasts, epithelial or T cells.