Abstract LB-350: IgG4 expressing B cells associate with poor survival in triple negative breast cancer

Abstract

Triple negative breast cancer (TNBC) is an aggressive form of breast cancer with high levels of lymphocyte infiltration. Although high levels of infiltrating B cells are present in TNBC, their role in progression of this disease is unclear. IgG4 is one of four subclasses of IgG and is the least abundant in healthy human serum. IgG4 has been found at higher percentages in both tissue and serum in cases of chronic inflammation, which promotes class switching to IgG4. Expression and secretion of IgG4 by B cells may be non-beneficial and potentially harmful in the cancer setting. Unlike the other subclasses of IgG, IgG4 does not activate complement dependent cytotoxicity and has a lower affinity for FcγR, thus resulting in a poor ability to engage immune effector cells and activate antibody-depended cell-mediated cytotoxicity. Additionally, IgG4 can compete with other IgG subclasses by binding to antigens and can sequestering IgG through Fc-Fc interactions, thus impairing potential anti-tumor antibody-mediated responses. As IgG4 expressing B cells have been shown to be associated with poor outcomes in other aggressive cancers such melanoma, glioblastoma and pancreatic cancer, we sought to determine the expression of IgG4 in TNBC. We performed immunohistological staining of IgG4 in paraffin-embedded tissue microarrays from 75 treatment-naive TNBC specimens obtained from women who underwent surgical resection of their tumors at the Helen F Graham Cancer Center and Research Institute from 2006-2007. We found that 69 % of TNBC cases contain IgG4+ cell infiltration. Moreover, the presence of IgG4+ cells is significantly correlated with poorer progression free (p<0.0003) and overall survival (p<0.0001) as determined by a Log-rank (Mantel-Cox) test. These findings indicate the presence of an immunosuppressive B cell population. Further study is needed to characterize these cells and to determine the significance of IgG4+ tumor infiltrating B cells, and their potential immunosuppressive role in the progression of TNBC. Citation Format: Nicole Flynn, Ugochukwu Amadi, Rajasekharan Somasundaram, Jennifer Sims-Mourtada. IgG4 expressing B cells associate with poor survival in triple negative breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr LB-350.