Seng Ryong Woo -, Leticia Corrales, Thomas F. Gajewski
A major subset of patients with advanced solid tumors show a spontaneous T cell-inflamed tumor microenvironment, which has prognostic import and is associated with clinical response to immunotherapies. As such, understanding the mechanisms governing the generation of spontaneous T cell responses in only a subset of patients is critical for advancing immunotherapeutic approaches further. Here, we discuss the characteristics of T cell-inflamed versus non-inflamed tumors, including a type I interferon (IFN) signature associated with T cell priming against tumor antigens. We review recent findings that have pointed towards the STING (stimulator of interferon genes) pathway of cytosolic DNA sensing as an important innate immune sensing mechanism driving type I IFN production in the tumor context. Knowledge of this pathway is guiding the further development of novel immunotherapeutic strategies.
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