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Immune activation b...
Immune activation by DNA damage predicts response to chemotherapy and survival in oesophageal adenocarcinoma
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Turkington, RC (author)
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Knight, LA (author)
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Blayney, JK (author)
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show more...
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Secrier, M (author)
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Douglas, R (author)
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Parkes, EE (author)
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Sutton, EK (author)
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Stevenson, L (author)
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McManus, D (author)
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Halliday, S (author)
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McCavigan, AM (author)
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Logan, GE (author)
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Walker, SM (author)
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Steele, CJ (author)
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Perner, J (author)
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Bornschein, J (author)
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MacRae, S (author)
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Miremadi, A (author)
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McCarron, E (author)
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McQuaid, S (author)
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Arthur, K (author)
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James, JA (author)
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Eatock, MM (author)
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O'Neill, R (author)
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Noble, F (author)
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Underwood, TJ (author)
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Harkin, DP (author)
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Salto-Tellez, M (author)
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Fitzgerald, RC (author)
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Kennedy, RD (author)
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Noorani, A (author)
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Edwards, PAW (author)
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Grehan, N (author)
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Nutzinger, B (author)
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Hughes, C (author)
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Fidziukiewicz, E (author)
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Crawte, J (author)
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Northrop, A (author)
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Contino, G (author)
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Li, XD (author)
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de la Rue, R (author)
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O'Donovan, M (author)
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Malhotra, S (author)
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Tripathi, M (author)
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Tavare, S (author)
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Lynch, AG (author)
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Eldridge, M (author)
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Bower, L (author)
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Devonshire, G (author)
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Jammula, S (author)
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Davies, J (author)
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Crichton, C (author)
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Carroll, N (author)
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Safranek, P (author)
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Hindmarsh, A (author)
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Sujendran, V (author)
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Hayes, SJ (author)
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Ang, Y (author)
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Preston, SR (author)
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Oakes, S (author)
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Bagwan, I (author)
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Save, V (author)
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Skipworth, RJE (author)
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Hupp, TR (author)
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Tucker, O (author)
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Beggs, A (author)
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Taniere, P (author)
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Puig, S (author)
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Owsley, J (author)
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Barr, H (author)
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Shepherd, N (author)
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Old, O (author)
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- Lagergren, J (author)
- Karolinska Institutet
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Gossage, J (author)
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Davies, A (author)
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Chang, FJ (author)
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Zylstra, J (author)
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Mahadeva, U (author)
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Goh, V (author)
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Ciccarelli, FD (author)
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Sanders, G (author)
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Berrisford, R (author)
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Harden, C (author)
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Lewis, M (author)
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Cheong, E (author)
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Kumar, B (author)
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Parsons, SL (author)
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Soomro, I (author)
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Kaye, P (author)
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Saunders, J (author)
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Lovat, L (author)
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Haidry, R (author)
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Igali, L (author)
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Scott, M (author)
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Sothi, S (author)
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Suortamo, S (author)
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Lishman, S (author)
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Hanna, GB (author)
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Moorthy, K (author)
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Peters, CJ (author)
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Grabowska, A (author)
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Coleman, H (author)
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(creator_code:org_t)
- 2019-03-09
- 2019
- English.
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In: Gut. - : BMJ. - 1468-3288 .- 0017-5749. ; 68:11, s. 1918-1927
- Related links:
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https://gut.bmj.com/...
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http://kipublication...
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https://doi.org/10.1...
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Abstract
Subject headings
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- Current 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.
Publication and Content Type
- ref (subject category)
- art (subject category)
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Gut
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To the university's database
- By the author/editor
-
Turkington, RC
-
Knight, LA
-
Blayney, JK
-
Secrier, M
-
Douglas, R
-
Parkes, EE
-
show more...
-
Sutton, EK
-
Stevenson, L
-
McManus, D
-
Halliday, S
-
McCavigan, AM
-
Logan, GE
-
Walker, SM
-
Steele, CJ
-
Perner, J
-
Bornschein, J
-
MacRae, S
-
Miremadi, A
-
McCarron, E
-
McQuaid, S
-
Arthur, K
-
James, JA
-
Eatock, MM
-
O'Neill, R
-
Noble, F
-
Underwood, TJ
-
Harkin, DP
-
Salto-Tellez, M
-
Fitzgerald, RC
-
Kennedy, RD
-
Noorani, A
-
Edwards, PAW
-
Grehan, N
-
Nutzinger, B
-
Hughes, C
-
Fidziukiewicz, E
-
Crawte, J
-
Northrop, A
-
Contino, G
-
Li, XD
-
de la Rue, R
-
O'Donovan, M
-
Malhotra, S
-
Tripathi, M
-
Tavare, S
-
Lynch, AG
-
Eldridge, M
-
Bower, L
-
Devonshire, G
-
Jammula, S
-
Davies, J
-
Crichton, C
-
Carroll, N
-
Safranek, P
-
Hindmarsh, A
-
Sujendran, V
-
Hayes, SJ
-
Ang, Y
-
Preston, SR
-
Oakes, S
-
Bagwan, I
-
Save, V
-
Skipworth, RJE
-
Hupp, TR
-
Tucker, O
-
Beggs, A
-
Taniere, P
-
Puig, S
-
Owsley, J
-
Barr, H
-
Shepherd, N
-
Old, O
-
Lagergren, J
-
Gossage, J
-
Davies, A
-
Chang, FJ
-
Zylstra, J
-
Mahadeva, U
-
Goh, V
-
Ciccarelli, FD
-
Sanders, G
-
Berrisford, R
-
Harden, C
-
Lewis, M
-
Cheong, E
-
Kumar, B
-
Parsons, SL
-
Soomro, I
-
Kaye, P
-
Saunders, J
-
Lovat, L
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Haidry, R
-
Igali, L
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Scott, M
-
Sothi, S
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Suortamo, S
-
Lishman, S
-
Hanna, GB
-
Moorthy, K
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Peters, CJ
-
Grabowska, A
-
Coleman, H
-
show less...
- Articles in the publication
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Gut
- By the university
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Karolinska Institutet