STING Signaling and Cancer: It is also known that inflammation can enhance the development of tumors. As an extension of our above work, we demonstrated that chronic STING signaling can fuel certain inflammation driven cancers (Ahn et al., Nature Communications 2014). Indeed, STING-deficient mice are significantly resistant to the development of tumors induced by chronic exposure to carcinogens. Nevertheless, transient STING activity is essential for protection of the host against microbial infection, for initiating tissue repair responses and for stimulating anti-tumor T cell activity (Barber G.N. Nature Reviews Immunology). Our research has indicated that DNA from dying tumor cells plays an important role in triggering extrinsic STING signaling in engulfing phagocytes (antigen presenting cells; APC’s) Extrinsic STING-dependent cytokine production in APC’s is essential for the efficient cross presentation of tumor cell antigens and the generation of anti-tumor T cell responses. STING-deficient mice do not efficiently generate anti-tumor T cell responses (Woo et al., Immunity 2014). However, tumor cells are notoriously non-immunogenic since their genomic DNA inefficiently actives STING in APC’s. Indeed, tumor cells mimic normal apoptotic cells following phagocytic engulfment and do not generate a robust immune response. This is because DNases in apoptotic cells (DNase III) and phagocytes (DNase II) ensure that all the dead cell’s DNA is degraded to avoid STING-dependent inflammation (Ahn et al., PNAS 2012). Subsequently, this knowledge has enabled our lab to develop new therapeutic approaches to overcome these obstacle and to make non-immunogenic tumor cells (cold) highly immunogenic (hot) using STING agonists [referred to as STAVs- STING activators] [Ahn et al., Cancer Cell, 2018]. The use of CDN’s are also being evaluated as immunotherapeutic anti-cancer agents, in the clinic.