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TILs Immunophenotype in Breast Cancer Predicts Local Failure and Overall Survival: Analysis in a Large Radiotherapy Trial with Long-Term Follow-Up

Aim: To determine the prognostic significance of the immunophenotype of tumour-infiltrating lymphocytes (TILs) within a cohort of breast cancer patients with long-term follow-up. Methods: Multiplexed immunofluorescence and automated image analysis were used to assess the expression of CD3, CD8, CD20...

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Autores principales: Millar, Ewan, Browne, Lois, Slapetova, Iveta, Shang, Fei, Ren, Yuqi, Bradshaw, Rachel, Ann Brauer, Heather, O’Toole, Sandra, Beretov, Julia, Whan, Renee, Graham, Peter H.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7563743/
https://www.ncbi.nlm.nih.gov/pubmed/32825588
http://dx.doi.org/10.3390/cancers12092365
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author Millar, Ewan
Browne, Lois
Slapetova, Iveta
Shang, Fei
Ren, Yuqi
Bradshaw, Rachel
Ann Brauer, Heather
O’Toole, Sandra
Beretov, Julia
Whan, Renee
Graham, Peter H.
author_facet Millar, Ewan
Browne, Lois
Slapetova, Iveta
Shang, Fei
Ren, Yuqi
Bradshaw, Rachel
Ann Brauer, Heather
O’Toole, Sandra
Beretov, Julia
Whan, Renee
Graham, Peter H.
author_sort Millar, Ewan
collection PubMed
description Aim: To determine the prognostic significance of the immunophenotype of tumour-infiltrating lymphocytes (TILs) within a cohort of breast cancer patients with long-term follow-up. Methods: Multiplexed immunofluorescence and automated image analysis were used to assess the expression of CD3, CD8, CD20, CD68, Fox P3, PD-1 and PD-L1 in a clinical trial of local excision and radiotherapy randomised to a cavity boost or not (n = 485, median follow-up 16 years). Kaplan–Meier and Cox multivariate analysis (MVA) methodology were used to ascertain relationships with local recurrence (LR), overall survival (OS) and disease-free survival (DFS). NanoString BC360 gene expression panel was applied to a subset of luminal patients to identify pathways associated with LR. Results: LR was predicted by low CD8 in MVA in the whole cohort (HR 2.34, CI 1.4–4.02, p = 0.002) and luminal tumours (HR 2.19, CI 1.23–3.92, p = 0.008) with associations with increased stromal components, decreased Tregs (FoxP3), inflammatory chemokines and SOX2. Poor OS was associated with low CD20 in the whole cohort (HR 1.73, CI 1.2–2.4, p = 0.002) and luminal tumours on MVA and low PD-L1 in triple-negative cancer (HR 3.44, CI 1.5–7, p = 0.003). Conclusions: Immunophenotype adds further prognostic data to help further stratify risk of LR and OS even in TILs low-luminal tumours.
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spelling pubmed-75637432020-10-27 TILs Immunophenotype in Breast Cancer Predicts Local Failure and Overall Survival: Analysis in a Large Radiotherapy Trial with Long-Term Follow-Up Millar, Ewan Browne, Lois Slapetova, Iveta Shang, Fei Ren, Yuqi Bradshaw, Rachel Ann Brauer, Heather O’Toole, Sandra Beretov, Julia Whan, Renee Graham, Peter H. Cancers (Basel) Article Aim: To determine the prognostic significance of the immunophenotype of tumour-infiltrating lymphocytes (TILs) within a cohort of breast cancer patients with long-term follow-up. Methods: Multiplexed immunofluorescence and automated image analysis were used to assess the expression of CD3, CD8, CD20, CD68, Fox P3, PD-1 and PD-L1 in a clinical trial of local excision and radiotherapy randomised to a cavity boost or not (n = 485, median follow-up 16 years). Kaplan–Meier and Cox multivariate analysis (MVA) methodology were used to ascertain relationships with local recurrence (LR), overall survival (OS) and disease-free survival (DFS). NanoString BC360 gene expression panel was applied to a subset of luminal patients to identify pathways associated with LR. Results: LR was predicted by low CD8 in MVA in the whole cohort (HR 2.34, CI 1.4–4.02, p = 0.002) and luminal tumours (HR 2.19, CI 1.23–3.92, p = 0.008) with associations with increased stromal components, decreased Tregs (FoxP3), inflammatory chemokines and SOX2. Poor OS was associated with low CD20 in the whole cohort (HR 1.73, CI 1.2–2.4, p = 0.002) and luminal tumours on MVA and low PD-L1 in triple-negative cancer (HR 3.44, CI 1.5–7, p = 0.003). Conclusions: Immunophenotype adds further prognostic data to help further stratify risk of LR and OS even in TILs low-luminal tumours. MDPI 2020-08-21 /pmc/articles/PMC7563743/ /pubmed/32825588 http://dx.doi.org/10.3390/cancers12092365 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Millar, Ewan
Browne, Lois
Slapetova, Iveta
Shang, Fei
Ren, Yuqi
Bradshaw, Rachel
Ann Brauer, Heather
O’Toole, Sandra
Beretov, Julia
Whan, Renee
Graham, Peter H.
TILs Immunophenotype in Breast Cancer Predicts Local Failure and Overall Survival: Analysis in a Large Radiotherapy Trial with Long-Term Follow-Up
title TILs Immunophenotype in Breast Cancer Predicts Local Failure and Overall Survival: Analysis in a Large Radiotherapy Trial with Long-Term Follow-Up
title_full TILs Immunophenotype in Breast Cancer Predicts Local Failure and Overall Survival: Analysis in a Large Radiotherapy Trial with Long-Term Follow-Up
title_fullStr TILs Immunophenotype in Breast Cancer Predicts Local Failure and Overall Survival: Analysis in a Large Radiotherapy Trial with Long-Term Follow-Up
title_full_unstemmed TILs Immunophenotype in Breast Cancer Predicts Local Failure and Overall Survival: Analysis in a Large Radiotherapy Trial with Long-Term Follow-Up
title_short TILs Immunophenotype in Breast Cancer Predicts Local Failure and Overall Survival: Analysis in a Large Radiotherapy Trial with Long-Term Follow-Up
title_sort tils immunophenotype in breast cancer predicts local failure and overall survival: analysis in a large radiotherapy trial with long-term follow-up
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7563743/
https://www.ncbi.nlm.nih.gov/pubmed/32825588
http://dx.doi.org/10.3390/cancers12092365
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