Fig. 3

cGAS/STING pathway as driver of senescence and immunosurveillance

(1) Upon binding to cytosolic dsDNA, cGAS drives the production of cGAMP that is detected by STING on ER membrane. Then, STING transfers to the Golgi apparatus and recruits TBK1 and IκB kinases to activate IRF3 and NF-κB, respectively, giving rise to the production of type I IFNs and a plethora of inflammatory cytokines and chemokines that are secreted in the extracellular milieu representing the SASP components. (2) SASP factors promote autocrine and paracrine senescence, moreover they contribute to immune cell recruitment and activation favoring the elimination of cancer senescent cells. (3) Sustained cGAS/STING activation over time, following accumulation of cytosolic dsDNA in senescent cancer cells, determines the persistence of a pro-inflammatory and pro-tumoral SASP favoring the generation of immunosuppressive populations that negatively affect cancer immunosurveillance.

Abbreviations: Treg (T regulatory cells); MDSC (Myeloid Suppressor Cells); iDC (immature Dendritic Cells)

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