Fig. 7: Harnessing anti-tumor immunity with STING agonists overcomes immune suppression and resistance to PARP inhibition in BRCA1-deficient breast cancer.

BRCA1-deficient breast tumors elicit pro-tumorigenic macrophage polarization. In turn, these tumor-educated macrophages not only exhibit suppressive activity against T cells, but also attenuate PARPi-mediated synthetic lethality and the production of double-stranded DNA (dsDNA) fragments, thus diminishing the activation of the DNA sensing adaptor STING and rendering BRCA1-deficient breast tumors resistant to PARPi therapy (blue shading). Exogenous agonists of the STING pathway reprogram the macrophages and trigger innate immune activation of both macrophages and DCs, potentiating PARPi therapy to induce tumor cell DNA damage and an adaptative immune response that re-sensitizes tumors to PARPi therapy (orange shading).