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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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Detalles Bibliográficos
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
Descripción
Sumario: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.