Figure 1

Macrophages and T cells in the tumor micro milieu. Tumors actively attract myeloid cells by the secretion of chemokines which is amongst others driven by hypoxia (I). Once myeloid cells have arrived in the tumor micro milieu several tumor cell produced factors drive the differentiation into a range of different types of macrophages, including M2 macrophages as a consequence of high STAT3 phosphorylation (II). M2 macrophages produce tumor promoting factors, express inhibitory molecules and upon activation produce anti-inflammatory cytokines and metalloproteinase that hamper T-cell function and promote tumor growth (III). Activation of M2 macrophages in the presence of IFNγ - for instance following cognate interaction CD4+ type 1 helper T cells - switch M2 macrophages to pro-inflammatory activated M1 macrophages (IV). M1 macrophages alter the immune suppressed micro milieu by producing IL-12 helping anti-tumor T cells as well as directly attack tumor cells (V).