Abstract 7360: Characterizing the immune microenvironment of Nigerian breast tumors by subtype

Abstract Background: Breast cancer (BC) bears significant and well-established disparities in aggressiveness and mortality, disproportionally affecting women of African descent. While socioeconomic factors might explain disparities in BC outcomes in women of African descent, intrinsic tumor biology is now recognized as a contributing factor in BC mortality. Clinical and molecular features of breast tumors in African American women strikingly resemble those of West African women, both characterized by early onset and a high prevalence of the aggressive triple-negative breast cancer subtype, suggesting the shared West African genetic ancestry might play a factor in BC aggressiveness. However, there is a paucity of studies that have clearly characterized the breast tumor microenvironment (TME) in West African women, a critical knowledge gap whose addressing might open therapeutic opportunities to address BC disparities in women of African descent. In this study, we characterized the immune repertoire of BC from Nigeria by receptor subtype. Methods: We used the Nanostring technology Immune Exhaustion (IE) Panel to characterize the immune repertoire of Nigerian breast tumors by subtype. The Nanostring IE panel targets 785 genes across 47 pathways involved in immune activation, suppression, exhaustion and memory. RNA was isolated from breast tumors of 48 newly diagnosed, treatment naïve breast cancer patients with either estrogen receptor-positive (ER+), HER2-enriched, and Triple-negative Breast Cancer (TNBC) subtypes from Nigeria. After hybridization of the RNA with fluorescent barcoded IE panel probes and counting of hybridized probes, quality control and normalization of the raw data were performed using the Nanostring nSolver Software. Analysis of differential gene expression, pathway scoring, cell type profiling, and gene set enrichment by receptor subtype was performed using the nSolver Software Advanced Analysis Package 2.0, NanostringTM). Results: Six differentially expressed genes (DEGs) were significantly upregulated or downregulated in ER+ breast cancers vs TNBC. The CHRD gene (associated with TGF-beta signaling) was the most significantly upregulated in ER+ BC vs TNBC. In contrast, the SHC4 gene (associated with cytotoxicity) was the most significantly downregulated in ER+BC vs TNBC. Pathway scoring indicated that ER+ BC had decreased fatty acid metabolism, hypoxia response, and glycolysis and glucose import pathway scores compared to TNBC. No differences in B, T, and NK cell immune exhaustion scores were observed between various BC subtypes. Conclusion: We observed differences in gene expression and metabolic pathways by subtypes, with the ER+ BC subtype having lower fatty acid metabolism, and glycolysis and glucose import pathway scores in comparison to TNBC. Our findings highlight new insights that could open therapeutic opportunities to improve BC outcomes among women of African descent. Citation Format: Jovita Byemerwa, Drew Neish, April Deveaux, Omolola Salako, Adetola Daramola, Olusegun Alatise, Gabriel Egun, Tomi Akinyemiju. Characterizing the immune microenvironment of Nigerian breast tumors by subtype [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 7360.