ArticleGut2019
Immune activation by DNA damage predicts response to chemotherapy and survival in oesophageal adenocarcinoma.
Article in Gut, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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19 citing papers in PubMed, 27 citations in OpenAlex.
- AXL: shapers of tumor progression and immunosuppressive microenvironments.Molecular cancer · 2025Review
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- Inhibition of AKT enhances chemotherapy efficacy and synergistically interacts with targeting of the Inhibitor of apoptosis proteins in oesophageal adenocarcinoma.Scientific reports · 2024Article
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- Expression of MxA in esophageal cancer cell lines can influence sensitivity to chemotherapeutic agents but this does not require apoptosis.Cancer medicine · 2024Article
- DNA damage response-related immune activation signature predicts the response to immune checkpoint inhibitors: from gastrointestinal cancer analysis to pan-cancer validation.Cancer biology & medicine · 2023Article
- Association of immune-related expression profile with sensitivity to chemotherapy in esophageal squamous cell carcinoma.Cancer science · 2023Article
- Preexisting Immunity Drives the Response to Neoadjuvant Chemotherapy in Esophageal Adenocarcinoma.Cancer research · 2023Article
- Article
- Resistance to immune checkpoint inhibitors in advanced gastro-oesophageal cancers.British journal of cancer · 2021Review
- Genomic Analysis of Response to Neoadjuvant Chemotherapy in Esophageal Adenocarcinoma.Cancers · 2021Article
- A DNA-damage immune response assay combined with PET biomarkers predicts response to neo-adjuvant chemotherapy and survival in oesophageal adenocarcinoma.Scientific reports · 2021Article
- Prediction of lymph node metastases using pre-treatment PET radiomics of the primary tumour in esophageal adenocarcinoma: an external validation study.The British journal of radiology · 2021Article
- Derivation and Application of Molecular Signatures to Prostate Cancer: Opportunities and Challenges.Cancers · 2021Review
- In-depth Clinical and Biological Exploration of DNA Damage Immune Response as a Biomarker for Oxaliplatin Use in Colorectal Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2021Article
- Transcriptomic biomarkers for predicting response to neoadjuvant treatment in oesophageal cancer.Gastroenterology report · 2020Review
- Linking Circulating Serum Proteins with Clinical Outcomes in Esophageal Adenocarcinoma-An Emerging Role for Chemokines.Cancers · 2020Article
- A Review on Curability of Cancers: More Efforts for Novel Therapeutic Options Are Needed.Cancers · 2019Review
- Supplementary granulocyte macrophage colony-stimulating factor to chemotherapy and programmed death-ligand 1 blockade decreases local recurrence after surgery in bladder cancer.Cancer science · 2019Article
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Authors and funding
31 authors at 11 institutions in 1 country.
Funding
Abstract
objectiveCurrent strategies to guide selection of neoadjuvant therapy in oesophageal adenocarcinoma (OAC) are inadequate. We assessed the ability of a DNA damage immune response (DDIR) assay to predict response following neoadjuvant chemotherapy in OAC.
designTranscriptional profiling of 273 formalin-fixed paraffin-embedded prechemotherapy endoscopic OAC biopsies was performed. All patients were treated with platinum-based neoadjuvant chemotherapy and resection between 2003 and 2014 at four centres in the Oesophageal Cancer Clinical and Molecular Stratification consortium. CD8 and programmed death ligand 1 (PD-L1) immunohistochemical staining was assessed in matched resection specimens from 126 cases. Kaplan-Meier and Cox proportional hazards regression analysis were applied according to DDIR status for recurrence-free survival (RFS) and overall survival (OS).
resultsA total of 66 OAC samples (24%) were DDIR positive with the remaining 207 samples (76%) being DDIR negative. DDIR assay positivity was associated with improved RFS (HR: 0.61; 95% CI 0.38 to 0.98; p=0.042) and OS (HR: 0.52; 95% CI 0.31 to 0.88; p=0.015) following multivariate analysis. DDIR-positive patients had a higher pathological response rate (p=0.033), lower nodal burden (p=0.026) and reduced circumferential margin involvement (p=0.007). No difference in OS was observed according to DDIR status in an independent surgery-alone dataset.DDIR-positive OAC tumours were also associated with the presence of CD8+ lymphocytes (intratumoural: p<0.001; stromal: p=0.026) as well as PD-L1 expression (intratumoural: p=0.047; stromal: p=0.025).
conclusionThe DDIR assay is strongly predictive of benefit from DNA-damaging neoadjuvant chemotherapy followed by surgical resection and is associated with a proinflammatory microenvironment in OAC.
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