Abstract PO4-09-09: Deep Immunoprofiling Demonstrates Racial Differences in the Peripheral Immune System in Women at Risk for Breast Cancer

Abstract

Abstract Background: Disparities in breast cancer outcomes between Non-Hispanic Black (NHB) and Non-Hispanic White (NHW) women have been attributed to NHB women presenting with more aggressive subtypes and later stage disease, differences in treatment receipt and adherence, access to care and tumor biology. However, previous work has shown that these known factors do not fully account for the observed disparities in outcomes. Systemic immune fitness is a factor not previously studied that may play a role in dictating disease progression and therapeutic responses. Numerous factors, including age and race, impact immune system function and understanding these changes is critical to address disparities in breast cancer outcomes. Here, we developed a pipeline for deep immunoprofiling of peripheral blood mononuclear cells (PBMC) at single cell resolution by full-spectrum flow cytometry. Using this pipeline, we sought to investigate whether there are differences in immune fitness between NHB and NHW women at high risk for developing breast cancer. Methods: PBMC were collected and processed from age-matched NHB and NHW women (n=20/cohort) identified as being at high risk for developing breast cancer through our institution’s B-PREP (Breast Cancer Personalized Risk Assessment Education and Prevention) clinic. Two custom antibody panels and protocols for comprehensive immunoprofiling of T and B cell subsets (T/B Panel), as well as monocytic, NK, and dendritic cell subsets (M/N/D Panel), along with functional and exhaustion markers were designed, optimized, and implemented. Traditional gating strategies were used to quantify proportions of canonical cell populations, and unbiased high dimensionality reduction analysis was performed using the OMIQ analysis platform to assess phenotypes and functional status of various immune cell subsets. Results: Significant differences between cohorts in abundance as well as phenotype of various cell populations were observed. Specifically, CD4+ follicular helper T cells, TEMRA CD8, and CD45RA Terminal Effector CD8+ cells were enriched in NHB women while PD-1+/CD3+ cells and PD-1+/CD8+ cells were enriched in the NHW women (Table). Additionally, several immunosuppressive and systemic inflammatory immune cell types were enriched in NHB women (Table). Conclusions: Deep immunoprofiling using single-cell spectral flow cytometry revealed differences in peripheral immune cells between NHB and NHW women at high risk for breast cancer. The significant enrichment of immunosuppressive monocytes and several activated NK cell populations in PBMC samples from NHB women relative to those from NHW women indicate an altered immune environment that may influence breast cancer development. Additional analysis, including a larger sample size and patients with invasive cancer, are ongoing to further understand if differences in immune fitness between NHB and NHW women are associated with disparities in breast cancer outcomes. Table: PBMC populations (% of CD45+) that are significantly enriched in NHB relative to NHW patients Citation Format: Esther Ogayo, Milos Spasic, Tasnim Rahman, Olga Kantor, Tari King, Peter van Galen, Sandra McAllister, Elizabeth Mittendorf. Deep Immunoprofiling Demonstrates Racial Differences in the Peripheral Immune System in Women at Risk for Breast Cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-09-09.