dc.contributor.author | Challoner, BR | |
dc.contributor.author | von Loga, K | |
dc.contributor.author | Woolston, A | |
dc.contributor.author | Griffiths, B | |
dc.contributor.author | Sivamanoharan, N | |
dc.contributor.author | Semiannikova, M | |
dc.contributor.author | Newey, A | |
dc.contributor.author | Barber, LJ | |
dc.contributor.author | Mansfield, D | |
dc.contributor.author | Hewitt, LC | |
dc.contributor.author | Saito, Y | |
dc.contributor.author | Davarzani, N | |
dc.contributor.author | Starling, N | |
dc.contributor.author | Melcher, A | |
dc.contributor.author | Grabsch, HI | |
dc.contributor.author | Gerlinger, M | |
dc.date.accessioned | 2020-04-02T10:39:09Z | |
dc.date.issued | 2021-01-04 | |
dc.identifier.citation | Journal of the National Cancer Institute, 2021, 113 (1), pp. 88 - 98 | |
dc.identifier.issn | 0027-8874 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/3571 | |
dc.identifier.eissn | 1460-2105 | |
dc.identifier.doi | 10.1093/jnci/djaa051 | |
dc.description.abstract | BACKGROUND: Gastric and gastro-esophageal junction cancers (GCs) frequently recur after resection, but markers to predict recurrence risk are missing. T-cell infiltrates have been validated as prognostic markers in other cancer types, but not in GC because of methodological limitations of past studies. We aimed to define and validate the prognostic role of major T-cell subtypes in GC by objective computational quantification. METHODS: Surgically resected chemotherapy-naïve GCs were split into discovery (n = 327) and validation (n = 147) cohorts. CD8 (cytotoxic), CD45RO (memory), and FOXP3 (regulatory) T-cell densities were measured through multicolor immunofluorescence and computational image analysis. Cancer-specific survival (CSS) was assessed. All statistical tests were two-sided. RESULTS: CD45RO-cell and FOXP3-cell densities statistically significantly predicted CSS in both cohorts. Stage, CD45RO-cell, and FOXP3-cell densities were independent predictors of CSS in multivariable analysis; mismatch repair (MMR) and Epstein-Barr virus (EBV) status were not statistically significant. Combining CD45RO-cell and FOXP3-cell densities into the Stomach Cancer Immune Score showed highly statistically significant (all P ≤ .002) CSS differences (0.9 years median CSS to not reached). T-cell infiltrates were highest in EBV-positive GCs and similar in MMR-deficient and MMR-proficient GCs. CONCLUSION: The validation of CD45RO-cell and FOXP3-cell densities as prognostic markers in GC may guide personalized follow-up or (neo)adjuvant treatment strategies. Only those 20% of GCs with the highest T-cell infiltrates showed particularly good CSS, suggesting that a small subgroup of GCs is highly immunogenic. The potential for T-cell densities to predict immunotherapy responses should be assessed. The association of high FOXP3-cell densities with longer CSS warrants studies into the biology of regulatory T cells in GC. | |
dc.format | Print | |
dc.format.extent | 88 - 98 | |
dc.language | eng | |
dc.language.iso | eng | |
dc.publisher | OXFORD UNIV PRESS INC | |
dc.rights.uri | https://creativecommons.org/licenses/by-nc/4.0 | |
dc.title | Computational Image Analysis of T-Cell Infiltrates in Resectable Gastric Cancer: Association with Survival and Molecular Subtypes. | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2020-04-02 | |
rioxxterms.versionofrecord | 10.1093/jnci/djaa051 | |
rioxxterms.licenseref.uri | https://creativecommons.org/licenses/by-nc/4.0 | |
rioxxterms.licenseref.startdate | 2021-01 | |
rioxxterms.type | Journal Article/Review | |
dc.relation.isPartOf | Journal of the National Cancer Institute | |
pubs.issue | 1 | |
pubs.notes | No embargo | |
pubs.organisational-group | /ICR | |
pubs.organisational-group | /ICR/Primary Group | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Cancer Biology | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Cancer Biology/Targeted Therapy | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Clinical Studies | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Clinical Studies/Gastrointestinal Cancers Clinical Trials | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Clinical Studies/Gastrointestinal Cancers Clinical Trials/Gastrointestinal Cancers Clinical Trials (hon.) | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Molecular Pathology | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Molecular Pathology/Translational Oncogenomics | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging/Targeted Therapy | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging/Translational Immunotherapy | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging/Translational Immunotherapy/Translational Immunotherapy (TL) | |
pubs.organisational-group | /ICR/Primary Group/Royal Marsden Clinical Units | |
pubs.organisational-group | /ICR/Students | |
pubs.organisational-group | /ICR/Students/PhD and MPhil | |
pubs.organisational-group | /ICR/Students/PhD and MPhil/16/17 Starting Cohort | |
pubs.organisational-group | /ICR/Students/PhD and MPhil/18/19 Starting Cohort | |
pubs.organisational-group | /ICR/Students/PhD and MPhil/19/20 Starting Cohort | |
pubs.publication-status | Published | |
pubs.volume | 113 | |
pubs.embargo.terms | No embargo | |
icr.researchteam | Gastrointestinal Cancers Clinical Trials | |
icr.researchteam | Translational Oncogenomics | |
icr.researchteam | Targeted Therapy | |
icr.researchteam | Translational Immunotherapy | |
dc.contributor.icrauthor | Challoner, Benjamin | |
dc.contributor.icrauthor | Woolston, Andrew | |
dc.contributor.icrauthor | Semiannikova, Maria | |
dc.contributor.icrauthor | Newey, Alice | |
dc.contributor.icrauthor | Mansfield, David | |
dc.contributor.icrauthor | Melcher, Alan | |
dc.contributor.icrauthor | Gerlinger, Marco | |