B cells enhance IL-1 beta driven invasiveness in triple negative breast cancer
Nicole J. Toney, Lynn M. Opdenaker, Lisa Frerichs, Shirin Modarai, Aihui Ma, Holly Archinal, Grace O. Ajayi, Jennifer Sims‐Mourtada
Abstract
Triple-negative breast cancer (TNBC) is an aggressive subtype often characterized by high lymphocyte infiltration, including tumor-infiltrating B cells (TIBs). These cells are present even in early stages of TNBC and associated with microinvasion. This study shows that co-culturing TNBC cells with B cells increases Interleukin-1β (IL-1β) expression and secretion. We further show that B cell-induced IL-1β activates NFκB signaling, leading to higher expression of target genes and promoting IL-1β-dependent increases in matrix metalloproteinase (MMP) activity, invasion, and migration. Immunohistochemical analysis of IL-1β and TIBs in triple-negative ductal carcinoma in situ (DCIS, n = 90) and invasive TNBC (n = 171) revealed that in DCIS, TIBs correlated with IL-1β expression and microinvasion, with IL-1β also linked to recurrence. In invasive TNBC, IL-1β expression correlated with TIB density and stage, with high IL-1β levels associated with poorer survival outcomes. These findings suggest that early B cell presence in TNBC can induce IL-1β secretion, enhancing invasion and mobility through IL-1β-NFκB signaling. This highlights the potential of IL-1 inhibitors as preventive and therapeutic options for hormone receptor-negative DCIS and TNBC.