Dissecting the immune infiltrate of primary luminal B-like breast carcinomas in relation to age.
(luminal) breast cancer
aging
breast cancer biology
immune infiltration
multiplex immunohistochemistry
spatial proteomics
tumor (immune) microenvironment
Journal
The Journal of pathology
ISSN: 1096-9896
Titre abrégé: J Pathol
Pays: England
ID NLM: 0204634
Informations de publication
Date de publication:
29 Sep 2024
29 Sep 2024
Historique:
revised:
26
06
2024
received:
17
01
2024
accepted:
24
08
2024
medline:
30
9
2024
pubmed:
30
9
2024
entrez:
30
9
2024
Statut:
aheadofprint
Résumé
The impact of aging on the immune landscape of luminal breast cancer (Lum-BC) is poorly characterized. Understanding the age-related dynamics of immune editing in Lum-BC is anticipated to improve the therapeutic benefit of immunotherapy in older patients. To this end, here we applied the 'multiple iterative labeling by antibody neo-deposition' (MILAN) technique, a spatially resolved single-cell multiplex immunohistochemistry method. We created tissue microarrays by sampling both the tumor center and invasive front of luminal breast tumors collected from a cohort of treatment-naïve patients enrolled in the prospective monocentric IMAGE (IMmune system and AGEing) study. Patients were subdivided into three nonoverlapping age categories (35-45 = 'young', n = 12; 55-65 = 'middle', n = 15; ≥70 = 'old', n = 26). Additionally, depending on localization and amount of cytotoxic T lymphocytes, the tumor immune types 'desert' (n = 22), 'excluded' (n = 19), and 'inflamed' (n = 12) were identified. For the MILAN technique we used 58 markers comprising phenotypic and functional markers allowing in-depth characterization of T and B lymphocytes (T&B-lym). These were compared between age groups and tumor immune types using Wilcoxon's test and Pearson's correlation. Cytometric analysis revealed a decline of the immune cell compartment with aging. T&B-lym were numerically less abundant in tumors from middle-aged and old compared to young patients, regardless of the geographical tumor zone. Likewise, desert-type tumors showed the smallest immune-cell compartment and were not represented in the group of young patients. Analysis of immune checkpoint molecules revealed a heterogeneous geographical pattern of expression, indicating higher numbers of PD-L1 and OX40-positive T&B-lym in young compared to old patients. Despite the numerical decline of immune infiltration, old patients retained higher expression levels of OX40 in T helper cells located near cancer cells, compared to middle-aged and young patients. Aging is associated with important numerical and functional changes of the immune landscape in Lum-BC. © 2024 The Author(s). The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Emmanuel Van der Schueren
Organisme : Fonds Voor Wetenschappelijk Onderzoek Vlaanderen
ID : 1802211N
Informations de copyright
© 2024 The Author(s). The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.
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