Cytosolic DNA accumulation promotes breast cancer immunogenicity via a STING-independent pathway

Immune checkpoint blockade (ICB) has revolutionized cancer treatment. However, ICB alone has demonstrated only benefit in a small subset of patients with breast cancer. We here reported that the tumoral cytosolic ssDNA is associated with tumor-infiltrating lymphocyte in patients with triple negative breast cancer. TREX1 deficiency triggered a STING-independent innate immune response via DDX3X. Cytosolic ssDNA accumulation in tumors due to TREX1 deletion is sufficient to drastically improve the efficacy of ICB. Overall design: RNA from control and TREX1-depleted tumors (via CRISPR-Cas9) treated with or without ICB were analyzed for global gene expression levels