Poster Presentation 36th Lorne Cancer Conference 2024

Age-dependent changes in peripheral T cell phenotypes of early-stage breast cancer patients (#145)

Stefanie Stirl 1 2 , Michael L. Hun 1 2 , Kylie A. Clarke 1 , Megan M.R. O'Malley 1 2 , Luis E. Lara Gonzalez 1 2 , Michael A. Harris 1 2 , Jasmine Kay 1 2 , Valerie Setiono 1 , Paul Neeson 1 2 , Phillip K. Darcy 1 2 , Sherene Loi 1 2
  1. Cancer Research Division, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia
  2. Sir Peter MacCallum Department of Oncology, The University of Melbourne, Melbourne, VIC, Australia



Older age is associated with decreased immune function but younger patients present with more aggressive, higher-grade breast cancer (BC)1, and poorer response to immune checkpoint blockade2. We therefore investigated age-related differences in systemic immunity of early-stage breast cancer patients.


We collected peripheral blood mononuclear cells (PBMCs) from 132 early-stage BC patients, and subdivided them into young (≤39 years), middle-aged (40-59 years), and older (≥60 years) groups. Age-matched healthy donors were also analysed (n=15 per group). We investigated peripheral blood immune phenotypes of patients by age with multiparameter flow cytometric analysis, and correlations between peripheral blood and tumour through T cell receptor sequencing (TCR-seq) using genomic DNA.


Median age of our patient cohort was 48 (range 24-83), with 32 young (24%), 75 middle aged (57%), and 25 older (19%) patients. Subtype distribution was predominantly ER+/HER2- (51%), with samples mostly node positive (52%) and grade 3 (70%), and a median tumor size of 27.5 mm. Flow cytometry data showed significantly more CD8+ memory T cell subsets with older age (P<0.0001). Moreover, an increased inflammatory phenotype with significantly higher IFN-γ+ and TNF-α+ CD8+ T cells in older BC patients compared with healthy donors (TNF-α P=0.01) and younger BC patients (P<0.0001; both TNF-α and IFN-γ) was observed. There was also significantly decreased PD-1 expression in peripheral blood CD8+ T cells in older BC patients compared to their healthy counterparts (P=0.03). Through TCR-seq analysis, we identified a 10.5 fold increase in peripheral hyperexpanded TCRs (P<0.0001) and a 57% increase in overlap of TCRs from tumour-enriched clones and PBMCs (P=0.03) in older patients (n=6) compared with young (n=5). Clonal expansion of virus-specific T cells (e.g. EBV and CMV) in breast tumour tissue was also observed in both young and older patients. Due to low power, we did not segregate by subtype.


This study revealed significant differences in peripheral T cell immune responses to early-stage breast cancer with age which may account for the differential responses observed in young and older patients to immune checkpoint blockade. Further phenotypic and functional analysis of T cells from patients’ tumours is clearly warranted.  


  1. Kim, H. J., Kim, S., Freedman, R. A. & Partridge, A. H. The impact of young age at diagnosis (age below 40 years) on prognosis varies by breast cancer subtype: A U.S. SEER database analysis. Breast 61, 77-83, doi:10.1016/j.breast.2021.12.006 (2022).
  2. Adams, S. et al. Pembrolizumab monotherapy for previously untreated, PD-L1-positive, metastatic triple-negative breast cancer: cohort B of the phase II KEYNOTE-086 study. Ann Oncol 30, 405-411, doi:10.1093/annonc/mdy518 (2019).