Age-associated differences in the breast cancer immune microenvironment

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.