Subtype- and race-specific variations in the immune landscape of breast cancer: therapeutic implications.

Abstract

Breast cancer is a heterogeneous disease with distinct molecular subtypes that disproportionately affects Black women. Immune cells are a key component of the tumor microenvironment, influencing tumor growth and treatment outcomes. Here, we explored immune landscape differences between TNBC and non-TNBC subtypes, assessing any race-specific patterns. TNBC showed higher infiltration of B-cells, Treg cells, Th1 cells, and CD8+ cells, and fewer mast cells than non-TNBC. Race-wise comparisons revealed that White TNBC had more Th1 cells than Black TNBC, while Black non-TNBC exhibited higher NK and Treg cells but lower DCs. KEGG pathway analysis identified immunosuppression in TNBC, with Black patients exhibiting the same regardless of molecular subtype. Higher TAM and lower T-cell infiltration were linked to metastatic disease. In White patients, lower immune cells (particularly T-cells, DCs, and NK cells) correlated with more metastasis, but not in Black patients. These race- and subtype-specific immune differences may guide tailored immunotherapies.