| Title: |
Activation of a cGAS-STING-mediated immune response predicts response to neoadjuvant chemotherapy in early breast cancer |
| Authors: |
Parkes, EE; Savage, KI; Lioe, T; Boyd, C; Halliday, S; Walker, SM; Lowry, K; Knight, L; Buckley, NE; Grogan, A; Logan, GE; Clayton, A; Hurwitz, J; Kirk, SJ; Xu, J; Sidi, FA; Humphries, MP; Bingham, V; James, JA; James, CR; Paul Harkin, D; Kennedy, RD; McIntosh, SA |
| Publisher Information: |
Springer Nature [academic journals on nature.com] |
| Publication Year: |
2026 |
| Collection: |
Oxford University Research Archive (ORA) |
| Description: |
BACKGROUND: The DNA-damage immune-response (DDIR) signature is an immune-driven gene expression signature retrospectively validated as predicting response to anthracycline-based therapy. This feasibility study prospectively evaluates the use of this assay to predict neoadjuvant chemotherapy response in early breast cancer. METHODS: This feasibility study assessed the integration of a novel biomarker into clinical workflows. Tumour samples were collected from patients receiving standard of care neoadjuvant chemotherapy (FEC + /-taxane and anti-HER2 therapy as appropriate) at baseline, mid- and post-chemotherapy. Baseline DDIR signature scores were correlated with pathological treatment response. RNA sequencing was used to assess chemotherapy/response-related changes in biologically linked gene signatures. RESULTS: DDIR signature reports were available within 14 days for 97.8% of 46 patients (13 TNBC, 16 HER2 + ve, 27 ER + HER2-ve). Positive scores predicted response to treatment (odds ratio 4.67 for RCB 0-1 disease (95% CI 1.13-15.09, P = 0.032)). DDIR positivity correlated with immune infiltration and upregulated immune-checkpoint gene expression. CONCLUSIONS: This study validates the DDIR signature as predictive of response to neoadjuvant chemotherapy which can be integrated into clinical workflows, potentially identifying a subgroup with high sensitivity to anthracycline chemotherapy. Transcriptomic data suggest induction with anthracycline-containing regimens in immune restricted, "cold" tumours may be effective for immune priming. TRIAL REGISTRATION: Not applicable (non-interventional study). CRUK Internal Database Number 14232 |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| DOI: |
10.1038/s41416-021-01599-0 |
| Availability: |
https://doi.org/10.1038/s41416-021-01599-0; https://ora.ox.ac.uk/objects/uuid:395b9580-b17a-4ccf-a2ec-78577880f8c2 |
| Rights: |
info:eu-repo/semantics/openAccess ; CC Attribution (CC BY) |
| Accession Number: |
edsbas.F6D191A9 |
| Database: |
BASE |