Abstract P4-06-29: Prospective immune-profiling of locally advanced and metastatic breast cancer patients
Authors: BA Sezen, S Koca, O Alan, S Renzullo, FT Ozdemir, L Kozhaya, TA Telli, E Karhan, U Ugurlu, B Gulluoglu, F Dane, FP Yumuk, D Unutmaz
Journal: Cancer Research (2019)

Abstract Background: Breast cancer is still not curable with a substantial resistance rate in all subgroups. Alterations in immunological mechanisms are assumed to play a role in pathophysiology and potential efficiency of immunotherapy approaches. Understanding the immunological changes in these patients may have major implications as predictive biomarkers for disease progression. The aim of our study was to determine immune subsets and functions in patient blood between treatment naïve locally advanced and metastatic breast cancer at diagnosis and to compare it with multiple time points during and after different treatments. Subjects and Methods: The immunological profile of 25 stage II-III patients who were candidates for neoadjuvant treatment and 27 stage IV treatment naïve patients in two comprehensive oncology clinics (Marmara University and Medeniyet University, Istanbul, Turkey) were analyzed. Age-sex-matched healthy samples (n=26) were collected from volunteers. Peripheral blood mononuclear cells (PBMC) isolated from blood samples were frozen. PBMC were thawed and stained using multi parameter antibodies for immune profiling using flow cytometry in Jackson Laboratory, Farmington, CT. Results: Differences between T cell subsets among patients (metastatic and locally advanced group separately) and healthy controls were assessed. We found significant differences (all p values &amp;lt;0.01) in inflammatory and regulatory T cell subsets both among the two patient groups (metastatic vs locally advanced untreated)and vs healthy controls, at first time point blood samples: 1) Increase in memory CD4+ T cells (CD45RO+) proportions in both metastatic and locally advanced groups (2) Increase in central and effector CD8+ memory (CD45RO+ or CD45RO-CCR7-) T cells only in metastatic group compared to healthy and locally advanced group, 3) Increase regulatory T cells (Tregs) only in locally advanced group compared to healthy and metastatic patients, 4) Perturbations in proinflammatory Th17 cells in both patient groups compared to healthy controls. More extensive immune profiling of these groups and comparison of different time points during- and post-treatment and correlation with clinical data will be presented. Conclusions: Our results reveal significant differences in potential T cell activation and regulation in locally advanced and metastatic breast cancer patients, suggesting complex immune response at different disease stages. These findings have implications for as predictive indicators for disease progression for development of future immunotherapy strategies. Citation Format: Sezen BA, Koca S, Alan O, Renzullo S, Ozdemir FT, Kozhaya L, Telli TA, Karhan E, Ugurlu U, Gulluoglu B, Dane F, Yumuk FP, Unutmaz D. Prospective immune-profiling of locally advanced and metastatic breast cancer patients [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P4-06-29.