Age-associated differences in the breast cancer immune microenvironment.
6 affiliations
- 1Centre for Cancer Biomarkers CCBIO, Department of Clinical Medicine, University of Bergen, Bergen, Norway.
- 2Department of Pathology, Haukeland University Hospital, Bergen, Norway.
- 3Fürst Medical Laboratorium, Oslo, Norway.
- 4Faculty of Health Sciences, Oslo Metropolitan University, Oslo, Norway.
- 5Department of Pathology, Vestfold Hospital, Tønsberg, Norway.
- 6Department of Surgery, Haukeland University Hospital, Bergen, Bergen, Norway.
Abstract
Young age is associated with poorer outcomes and more aggressive clinicopathological features in breast cancer, but the biological underpinnings are incompletely understood. With the emergence of infiltrating immune cell tissue-based biomarkers, we aimed to investigate a relation to age by mapping of CD45, CD3, CD8, FOXP3, and CD163 positive cells. We examined a population-based cohort of women under the age of 50 years (BCY-B cohort, n = 311) in comparison to a previously reported series of patients aged 50-69 (TBC cohort, n = 282) years. The BCY-B cohort was additionally stained for two PD-L1 markers. Young age (under 50 years) was not associated with higher levels of tumor-infiltrating lymphocytes (TILs), represented by markers such as CD45 and CD3. However, younger patients presented with lower levels of FOXP3-positive TILs, both in luminal and non-luminal subgroups, and higher levels of CD163-positive tumor-associated macrophages (TAMs) in combined analyses only. CD163 showed prognostic value when analyzing all patients together and within the luminal subgroups. For non-luminal subgroups, CD3 expression was prognostic, while CD8 expression showed a trend. Notably, no age-associated difference in prognostic value was observed for any marker. Among patients within the BCY-B cohort (aged under 50 years), those below 40 years demonstrated higher PD-L1 tumor cell expression, also within the triple-negative subgroup, when compared to those aged 40-49 years. In conclusion, our study found only limited differences in tumor-infiltrating immune cells with age, with higher density of FOXP3-positive TILs in patients aged 50 years or above. Within the BCY-B cohort (age under 50), patients aged under 40 years showed higher tumor expression of PD-L1 when compared to those aged 40-49 years, suggesting age-associated differences in immune checkpoint regulation.
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BibTeX
@article{humlevik2026ageassociated,
title = {{Age-associated differences in the breast cancer immune microenvironment.}},
author = {Rasmus Oc Humlevik and Ying Chen and Tor A Klingen and Anna Km Sæle and Amalie A Svanøe and Ulrikke Hugaas and Amalie B Kvamme and Amalie F Tegnander and Ingeborg Winge and Turid Aas and Anette Heie and Lars A Akslen and Elisabeth Wik and Erling A Hoivik},
journal = {The journal of pathology. Clinical research},
year = {2026},
month = nov,
doi = {10.1002/2056-4538.70115},
url = {https://europepmc.org/article/MED/42975293},
note = {CC BY},
}
RIS
TY - JOUR
TI - Age-associated differences in the breast cancer immune microenvironment.
AU - Rasmus Oc Humlevik
AU - Ying Chen
AU - Tor A Klingen
AU - Anna Km Sæle
AU - Amalie A Svanøe
AU - Ulrikke Hugaas
AU - Amalie B Kvamme
AU - Amalie F Tegnander
AU - Ingeborg Winge
AU - Turid Aas
AU - Anette Heie
AU - Lars A Akslen
AU - Elisabeth Wik
AU - Erling A Hoivik
PY - 2026
DA - 2026/11/01
JO - The journal of pathology. Clinical research
DO - 10.1002/2056-4538.70115
UR - https://europepmc.org/article/MED/42975293
AB - Young age is associated with poorer outcomes and more aggressive clinicopathological features in breast cancer, but the biological underpinnings are incompletely understood. With the emergence of infiltrating immune cell tissue-based biomarkers, we aimed to investigate a relation to age by mapping of CD45, CD3, CD8, FOXP3, and CD163 positive cells. We examined a population-based cohort of women under the age of 50 years (BCY-B cohort, n = 311) in comparison to a previously reported series of patients aged 50-69 (TBC cohort, n = 282) years. The BCY-B cohort was additionally stained for two PD-L1 markers. Young age (under 50 years) was not associated with higher levels of tumor-infiltrating lymphocytes (TILs), represented by markers such as CD45 and CD3. However, younger patients presented with lower levels of FOXP3-positive TILs, both in luminal and non-luminal subgroups, and higher levels of CD163-positive tumor-associated macrophages (TAMs) in combined analyses only. CD163 showed prognostic value when analyzing all patients together and within the luminal subgroups. For non-luminal subgroups, CD3 expression was prognostic, while CD8 expression showed a trend. Notably, no age-associated difference in prognostic value was observed for any marker. Among patients within the BCY-B cohort (aged under 50 years), those below 40 years demonstrated higher PD-L1 tumor cell expression, also within the triple-negative subgroup, when compared to those aged 40-49 years. In conclusion, our study found only limited differences in tumor-infiltrating immune cells with age, with higher density of FOXP3-positive TILs in patients aged 50 years or above. Within the BCY-B cohort (age under 50), patients aged under 40 years showed higher tumor expression of PD-L1 when compared to those aged 40-49 years, suggesting age-associated differences in immune checkpoint regulation.
SN - 2056-4538
ER -