Figure 2. Different STAT proteins modulate pro-cancer and anti-tumour responses by myeloid cells.

Myeloid cells, such as dendritic cells (DCs) and macrophages, can stimulate anti-tumour T helper 1 (T_H1) adaptive immunity and even cause direct tumour cell death, which is associated with the production of T_H1 cytokines, including interleukin-12 (IL-12) and interferon-γ (IFNγ). Activation of signal transducer and activator of transcription 1 (STAT1) (p-STAT1 denotes the activated phosphorylated form of STAT1) and STAT4 is important for anti-tumour T_H1 responses. However, tumour-associated macrophages (TAMs) harbouring activated STAT3 (p-STAT3) no longer exhibit anti-tumour effects in the tumour microenvironment. Instead, along with myeloid-derived suppressor cells (MDSCs), TAMs promote cancer progression when STAT3 is activated. Moreover, STAT3 activity in the tumour microenvironment contributes to the expression of pro-cancer inflammatory mediators and angiogenic and growth factors, leading to increased tumour growth. Both activated STAT3 and STAT6 also promote MDSC expansion. Similar STAT3-dependent factors are produced by tumour cells and endothelial cells, forming a crosstalk network among tumour myeloid cells, tumour cells and tumour endothelial cells important for tumour angiogenesis and metastasis.