ArticleJournal for immunotherapy of cancer2023
Cytosolic DNA accumulation promotes breast cancer immunogenicity via a STING-independent pathway.
Article in Journal for immunotherapy of cancer, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed, 8 citations in OpenAlex.
- Chemotherapeutic induction of cytosolic single-stranded DNA accumulation sensitizes triple-negative breast cancer to immunotherapy.Journal for immunotherapy of cancer · 2026Article
- Targeting RNase H2: A dual-mechanism strategy to elevate replication stress, DNA damage, and antitumor immunity in TNBC.Cell reports. Medicine · 2026Article
- Disordered DNA-binding motif forms a modulation site for inhibiting the cancer immunotherapy target TREX1.Nucleic acids research · 2026Article
- Primary Malignant Melanoma of the Oesophagus Treated With Immunotherapy: A Case Report and Scoping Review of the Literature.Journal of gastrointestinal cancer · 2025Article
- Prevalence and impact of molecular variation in the three-prime repair exonuclease 1 TREX1 and its implications for oncology.Human genomics · 2025Article
- Discovering the Potential Role of the C2 DUSP2+ MCs Subgroup in Lung Adenocarcinoma.Translational oncology · 2025Article
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundImmune checkpoint blockade (ICB) has revolutionized cancer treatment. However, ICB alone has demonstrated only benefit in a small subset of patients with breast cancer. Recent studies have shown that agents targeting DNA damage response improve the efficacy of ICB and promote cytosolic DNA accumulation. However, recent clinical trials have shown that these agents are associated with hematological toxicities. More effective therapeutic strategies are urgently needed.
methodsPrimary triple negative breast cancer tumors were stained for cytosolic single-stranded DNA (ssDNA) using multiplex immunohistochemical staining. To increase cytosolic ssDNA, we genetically silenced TREX1. The role of tumor cytosolic ssDNA in promoting tumor immunogenicity and antitumor immune response was evaluated using murine breast cancer models.
resultsWe found the tumorous 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. We further identified a cytosolic ssDNA inducer CEP-701, which sensitized breast tumors to ICB without the toxicities associated with inhibiting DNA damage response.
conclusionsThis work demonstrated that cytosolic ssDNA accumulation promotes breast cancer immunogenicity and may be a novel therapeutic strategy to improve the efficacy of ICB with minimal toxicities.
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