Triple negative breast cancer (TNBC) is an aggressive form of breast cancer that progresses quickly from a non-invasive carcinoma in situ to an invasive state. Chronic inflammation associated to humoral immune responses has been found to promote aggressiveness in a number of solid tumor types. In breast cancer, B lymphocytes are associated with microinvasive disease and correlate with expression of inflammatory genes. The purpose of our work is to study the impact of B lymphocytes on the tumor microenvironment and increased invasiveness of TNBC cells. Through real-time PCR, we demonstrate that co-culture of B lymphocytes and TNBC cells leads to increased mRNA levels of IL1β and its downstream target interleukin 8 (IL8) in both B lymphocytes and in TNBC cells. Western Blot analysis shows that co-culture also leads to increased phosphorylation of p65, indicating IL-1 β activation of NFκB signaling. Additionally, co-culture of B lymphocytes with TNBC cells leads to increased expression of matrix metalloproteinases (MMPs) and cellular invasion through a matrigel invasion chamber. Gelatin zymography reveals increased functional MMP2 and MMP9 in tumor cell supernatant following co-culture with B lymphocytes. To complement our in vitro studies, we examined the presence of CD20+ B cells and expression of inflammatory cytokines IL-1β and IL-8 by immunohistochemistry in serial sections of tissue microarrays from patients with estrogen receptor (ER) positive and negative ductal carcinoma in situ (DCIS) and invasive carcinoma. Large areas of densely populated B cells were observed in ER-DCIS and in invasive TNBC compared to ER+ DCIS. Furthermore, in ER- DCIS and TNBC, both B lymphocytes and tumor cells are found to express IL1β whereas IL8 is found more specifically to be expressed by tumor cells. Our findings support the hypothesis that B lymphocytes promote a chronic inflammatory environment leading to increased invasion of TNBC cells.

Citation Format: Nicole Flynn, Rajasekharan Somasundaram, Jennifer Sims-Mourtada. B lymphocytes promote upregulation of an IL-1-NfkB dependent signaling and increase invasiveness of triple negative breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 650. doi:10.1158/1538-7445.AM2017-650