Abstract C110: Divergent immune surveillance in Black and White TNBC patients: Circulating and lymph node signatures

Abstract Triple-negative breast cancer (TNBC) disproportionately affects Black women, who face higher rates of aggressive disease and poorer outcomes. While tumor-intrinsic features have been studied, less is known about how immune surveillance and lymph node (LN) architecture differ by ethnicity. Anti-tumor immune responses typically begin in LNs through antigen presentation to naïve immune cells and executed by effector cells that circulate to and infiltrate tumors. We hypothesized that Black and White TNBC patients exhibit divergent immune signatures across both compartments. We first analyzed a retrospective cohort of 116 White, and 51 Black early-stage TNBC patients. Neutrophil and lymphocyte counts were extracted to assess systemic immune status. Black patients showed lower neutrophil-to-lymphocyte ratio (NLR; median 1.61 vs 2.71, p0.0001), consistent with ancestry-associated benign neutropenia. We next prospectively profiled immune signatures in early-stage TNBC patients. PBMCs from 55 patients (38 White, 17 Black) were analyzed by flow cytometry. Serum from 33 patients (20 White, 13 Black) was profiled using Olink proteomics, and 12 PBMCs by LC-MS. Immune profiling revealed coordinated alterations in both effector and antigen-presenting cell compartments (all padj0.05). Black patients had increased NK cells, particularly within the cytotoxic CD56dim and NKG2D+ subsets, and elevated dendritic cells skewed toward cross-presenting cDC1 subset. CD8+ T cells displayed reduced PD-1 expression and increased frequencies of both TEMRA and NKG2D+ subsets, suggesting enhanced cytotoxic potential. Circulating CD4+ central memory T cells were reduced, while CXCR5+CD4+ and CD8+ CM cells were elevated, potentially reflecting altered LN trafficking in black patients. Serum analysis showed elevated CXCL1/3 and TNF-α/NFκB signaling. LC-MS proteomics further indicated a shift toward oxidative phosphorylation in Black patients, suggesting distinct metabolic programming that may influence effector function. To examine immune architecture, we analyzed H0.05). A subset of 26 LNs (15 White, 11 Black) underwent 21-plex PhenoCycler analysis (∼12M cells). In uninvolved LNs, CD20+ zones in White patients had more CD8+ T cells, while Black patients had more naïve B cells and FDC-associated B cells. In involved LNs, White patients showed more CD8+ infiltration, while Black patients had fewer tumor–CD8+ contacts and more FOXP3+CD8+cells. These findings reveal ethnicity-linked divergence in immune surveillance, with Black patients displaying altered clinical indices, enhanced circulating effector features, but reduced CD8+ cytotoxic engagement in tumor-involved LNs. These systemic and spatial patterns may contribute to TNBC outcome disparities. Citation Format: Bryan Boon Han Ng, Paul Buckley, Helen Kakkassery, Thanussuyah Alaguthurai, Tara Chait, Rosalind Graham, Vedant Bhardwaj, Esme Carpenter, Melek Akay, Farhana Hossain, Patrycja Gazinska, Sheeba Irshad. Divergent immune surveillance in Black and White TNBC patients: Circulating and lymph node signatures abstract. In: Proceedings of the 18th AACR Conference on the Science of Cancer Health Disparities; 2025 Sep 18-21; Baltimore, MD. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2025;34(9 Suppl):Abstract nr C110.