TGF-β signalling in tumour associated macrophages

Tumour associated macrophages (TAM) represent an important component of tumour stroma. They develop under the influence of tumour microenvironment where transforming growth factor (TGF)β is frequently present. Activities of TAM regulated by TGFβ stimulate proliferation of tumour cells and lead to tumour immune escape. Despite high importance of TGFβ-induction of TAM activities till now our understanding of the mechanism of this induction is limited. We have previously developed a model of type 2 macrophages (M2) resembling certain properties of TAM. We established that in M2 TGFβRII is regulated on the level of subcellular sorting by glucocorticoids. Further studies revealed that in M2 with high levels of TGFβRII on the surface TGFβ activates not only its canonical Smad2/3-mediated signaling, but also Smad1/5-mediated signaling, what is rather typical for bone morphogenetic protein (BMP) stimulation. Complexity of macrophage populations, however, allows assumption that TGFβ signalling may function in different ways depending on the functional state of the cell. To understand the peculiarities of TGFβ signalling in human TAMs experimental systems using primary cells have to be developed and used together with the modern mathematical modelling approaches.