Figure 3.

Alternative STING pathway activation. High levels of DNA damage also activate the so called "alternative STING pathway" by ATM-TRAF6, inducing the production of IL-6 and transforming growth factor (TGF)-β generating the recruitment of protumor M2-like macrophages and regulatory T cells (Tregs). Furthermore, ATM-TRAF6 activates the transcription factor nuclear factor kB (NFkB) and induces tumor cell upregulation of PD-L1 that may elicit immune escape. Besides this mechanism, IFN type I itself (secreted upon STING activation) is the main factor inducing transcription and expression of PD-L1. STING = stimulator of interferon genes; PD-L1 = programmed cell death-ligand 1; IFN = interferon.