Activation of a cGAS-STING-mediated immune response predicts response to neoadjuvant chemotherapy in early breast cancer
| Autor: | Parkes, Eileen E., Savage, Kienan I., Lioe, Tong, Boyd, Clinton, Halliday, Sophia, Walker, Steven M., Lowry, Keith, Knight, Laura, Buckley, Niamh E., Grogan, Andrena, Logan, Gemma E., Clayton, Alison, Hurwitz, Jane, Kirk, Stephen J., Xu, Jiamei, Sidi, Fatima Abdullahi, Humphries, Matthew P., Bingham, Victoria, Ang, Melvyn, Askin, Conal, Bamford, Louise, Boyd, Ruth, Buckley, Miriam, Clarke, Jacqueline, Darragh, Lynn, Davis, Elaine, Foreman, Jennifer, Gallagher, Rebecca, Gill, Janine, Hanna, Michael, Hill, Naomi, Irwin, Gareth, Mallon, Peter, McAleer, Seamus, McAllister, Joanne, Morris, Melanie, Pierce, Nicole, Refsum, Sigi, Sloan, Samantha, Treanor, Sinead, James, Jacqueline, James, Colin R., Paul Harkin, D., Kennedy, Richard D., McIntosh, Stuart A. |
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| Jazyk: | angličtina |
| Rok vydání: | 2022 |
| Předmět: |
Adult
Bridged-Ring Compounds Oncology medicine.medical_specialty Cancer Research Anthracycline medicine.medical_treatment Antineoplastic Agents Breast Neoplasms Disease Predictive markers Article Breast cancer Immune system SDG 3 - Good Health and Well-being Internal medicine Biomarkers Tumor medicine Humans Pathological Chemotherapy business.industry Membrane Proteins Odds ratio Middle Aged medicine.disease Nucleotidyltransferases Neoadjuvant Therapy Gene Expression Regulation Neoplastic Treatment Outcome Biomarker (medicine) Female Taxoids Neoplasm Recurrence Local business DNA Damage |
| Zdroj: | Parkes, E E, Savage, K I, Lioe, T, Boyd, C, Halliday, S, Walker, S M, Lowry, K, Knight, L, Buckley, N E, Grogan, A, Logan, G E, Clayton, A, Hurwitz, J, Kirk, S J, Xu, J, Sidi, F A, Humphries, M P, Bingham, V, Ang, M, Askin, C, Bamford, L, Boyd, R, Buckley, M, Clarke, J, Darragh, L, Davis, E, Foreman, J, Gallagher, R, Gill, J, Hanna, M, Hill, N, Irwin, G, Mallon, P, McAleer, S, McAllister, J, Morris, M, Pierce, N, Refsum, S, Sloan, S, Treanor, S, James, J, James, C R, Paul Harkin, D, Kennedy, R D & McIntosh, S A 2022, ' Activation of a cGAS-STING-mediated immune response predicts response to neoadjuvant chemotherapy in early breast cancer ', British Journal of Cancer, vol. 126, no. 2, pp. 247-258 . https://doi.org/10.1038/s41416-021-01599-0 British Journal of Cancer |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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