Abstract 5358: A comparison of tumor microenvironment immune profiles using CIBERSORTx in breast cancer patients from Kenya and Hong Kong

Abstract Background: Tumor-infiltrating immune cells in the tumor microenvironment (TME) are critical for breast cancer (BC) progression and treatment outcomes, with notable variations observed across populations. Unique BC risk factors, such as germline genetics, mammographic density, infectious exposures, and lifestyle factors, may shape distinctive immune profiles and lead to distinct tumor characteristics and clinical outcomes in different populations. Comparing immune cell compositions across populations can improve our understanding of BC racial disparity and guide personalized treatment strategies. Aims: This study aims to characterize and compare immune composition in the BC TME between East Africa (Kenya) and East Asia (Hong Kong) when accounting for age, intrinsic subtype, and analytical methods. Methods: We collected formalin-fixed paraffin-embedded (FFPE) tumor blocks from BC patients in Kenya and Hong Kong, processed them for nucleic acid extraction and analyzed them using NanoString nCounter from a custom-designed code set including 50 PAM50 genes and 547 CIBERSORT panel genes. Samples were selected to match age and estrogen receptor (ER) status distributions. After removing duplicates and QC-failed samples, 467 samples from Kenya (mean age=50.57, ER+: 71.18%) and 118 samples from Hong Kong (mean age=54.94, ER+: 72.03%) were included in the subsequent analyses. CIBERSORTx was used to estimate relative fractions of 22 immune cell types. PAM50 subtype was defined as Luminal A, Luminal B, HER2-enriched, Basal-like, or Normal-like using the nearest centroid method. Multiple linear regression models were performed to identify the differences in immune cell proportions by ethnicity, adjusting for age, PAM50 subtype, and tumor grade. Results: After filtering cells with mean fractions <5%, this analysis was focused on T follicular helper, CD8+, resting CD4+, activated NK, resting mast, and macrophage subsets (M0, M1, M2). Compared to Hong Kong, Kenyan samples exhibited higher relative fractions of CD8+ T cells (p < 0.01), activated NK cells (p < 0.001), and macrophages M2 (p < 0.05) but lower fractions of resting CD4+ T cells (p < 0.05) and macrophages M0 (p < 0.01). Similar results were observed with absolute abundance analyses. Conclusion: This study reveals distinct immune profiles between Kenyan and Hong Kong BC TMEs. Kenyan samples exhibit a relatively “hot” immune TME with both pro-inflammatory and immunosuppressive components, while Hong Kong samples show a more quiescent or relatively “cold” immune environment. These population-specific differences highlight the potential need for tailored immunotherapy strategies considering unique immune characteristics shaped by genetic and environmental factors. Future analyses will explore associations with clinical outcomes and risk factors to elucidate mechanisms driving these racial disparities. Citation Format: Li Feng, Shahin Sayed, Hela Koka, Viviane Oluoch, Veronica Ngundo, Alfred M. Githuka, Zaitun Ajuoga, Kristine Jones, Belynda Hicks, Amy Hutchinson, Maria Brown, Petra Lenz, Aaron M. Rozeboom, Difei Wang, Francis Makokha, Stefan Ambs, Jonine Figueroa, Xiaohong R. Yang. A comparison of tumor microenvironment immune profiles using CIBERSORTx in breast cancer patients from Kenya and Hong Kong [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 5358.