Abstract P1-04-10: Breast cancer survivors exhibit an accumulation of CD4+ central memory T cells, a fall in CD8+ naïve T cells and higher activation of CD4+/CD8+ memory T cells in blood, which is positively correlated with age and fat mass index

Abstract

Abstract Introduction: T cells are important for tumour control and surveillance, but it is not well known how breast cancer treatment impacts their characteristics in blood. Methods: Healthy women (n=38, age 45 ± 11 y), breast cancer survivors (n=27, age 56 ± 6 y) and breast cancer patients (n=5, age 44 ± 9 y) took part. Survivors comprised women who had received any form of treatment for breast cancer within 1-2 years and were considered free from disease by their oncologist. Patients were recently diagnosed women scheduled to undergo neoadjuvant chemotherapy within 2 weeks. Using flow cytometry, CD4+ and CD8+ T cell subsets, including Naïve (NA), Central memory (CM) and Effector cells (EM and EMRA) were identified using CD27/CD45RA. Activation was measured by HLA-DR expression. Age, Cytomegalovirus (CMV) serostatus, cardiorespiratory fitness and body composition were assessed. Statistical analyses were conducted between healthy women and survivors. Data for patients enabled a qualitative interpretation of immune profiles at the time of diagnosis. Results: Lymphocyte, monocyte and neutrophil counts were not different between groups. However, compared to healthy women, CD4+ CM T cells were +Δ21% higher among survivors (cells/l: 417 ± 110 vs 346 ± 161, p=0.028) and CD8+ NA T cells were −Δ25% lower (cells/l: 106 ± 46 vs 142 ± 83, p=0.034). The proportion of activated (HLA-DR+) CD4+ and CD8+ T cell subsets was +Δ31% higher among survivors compared to healthy women: CD4+ CM (+Δ25%: 35 ± 16 % vs 28 ± 6 %), CD4+ EM (+Δ32%: 54 ± 17 % vs 41 ± 9 %) and CD4+ EMRA (+Δ43%: 53 ± 21 % vs 37 ± 11 %), total CD8+ (+Δ30%: 43 ± 18 % vs 33 ± 9 %), CD8+ EM (+Δ30%: 57 ± 18 % vs 44 ± 13 %) and CD8+ EMRA T cells (+Δ25%: 55 ± 21 % vs 44 ± 12 %) (p<0.046). Compared to healthy women, survivors were older (56 ± 6 y vs 45 ± 11 y), had lower cardiorespiratory fitness (VO2max mL•kg-1•min-1: 29.0 ± 5.1 vs 36.2 ± 8.5), had lower lean mass (42.3 ± 5.1 kg vs 48.4 ± 15.8 kg), had higher body fat (36.2 ± 5.4 % vs 32.7 ± 6.4 %) and higher fat mass index (FMI kg/m2: 9.5 ± 2.3 vs 8.1 ± 2.7) (all p<0.034). Among all participants, age positively correlated with activation levels of CD4+ EMRA and CD8+ EMRA T cells and FMI positively correlated with the proportion of activated CD4+ EMRA and CD8+ EM and EMRA T cells (Pearson r>0.277 p<0.036). CMV serostatus was not different between groups and did not influence results. Compared to healthy women and survivors, patients were younger (44 ± 9 y), had lower cardiorespiratory fitness (VO2max 27.3 ± 2.2 mL•kg-1•min-1), higher body fat (40 ± 5.8%) and higher FMI (11.2 ± 3.8 kg/m2). Lean mass (44.3 ± 4.4 kg) was higher than survivors but lower than healthy women. Patterns exhibited by survivors (compared to healthy women) tended to be present among patients (e.g. an accumulation of memory T cells and a decline in NA T cells). T cell activation was closer to the levels exhibited by healthy women. Conclusion: Breast cancer survivors exhibited signs of immunosenescence, including a decline in naïve T cells and accumulations of memory T cells, which exhibited higher activation levels. Among all participants, T cell activation was positively correlated with age and fat mass index, potentially contributing to systemic inflammation and a decline in immune competency. Citation Format: Ainhoa Arana Echarri, Lauren Struszczak, Mark Beresford, John P Campbell, Robert H Jones, Rachel Butler, Dylan Thompson, James E Turner. Breast cancer survivors exhibit an accumulation of CD4+ central memory T cells, a fall in CD8+ naïve T cells and higher activation of CD4+/CD8+ memory T cells in blood, which is positively correlated with age and fat mass index [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P1-04-10.