Abstract 455: B cells actively participate to the anti-cancer immune response in high grade serous ovarian cancer metastases
Authors: Anne Montfort, Steffen Boehm, Thomas Dowe, Joanne Topping, Michelle Lockley, Melania Capasso, Frances Balkwill
Journal: Cancer Research (2015)

Abstract Intra-tumor B cells and immunoglobulin signatures have been associated with a better clinical prognosis in ovarian cancer (Iglesia et al, 2014; Nielsen et al, 2012). However little is known about the mechanisms by which B cells influence the anti-cancer immune response. The aim of our research is to evaluate B cell dependent anti-cancer immune responses in peritoneal metastases in high grade serous ovarian cancer (HGSOC) patients. We have found that in these peritoneal metastases, B cells are mainly located in lymphoid structures and a high proportion of these (60%) display a CD27+ memory phenotype. HGSOC B cells are able to secrete Th1 related cytokines as well as high levels of IL8, which is a chemo-attractant for T cells, granulocytes and macrophages. Interestingly CD4+ and CD8+ T cells express high levels of the IL8 receptor, CXCR1, which suggests B cells help recruiting T cells to lymphoid structures. Plasma cells were also detected in the peritoneal metastases along with IgG deposits. Secreted IgGs were mainly located in stromal areas suggesting that the associated matrix may prevent their infiltration into tumour islets and/or that they target specific stromal antigens. Interestingly, we observed that neoadjuvant chemotherapy and residual disease after chemotherapy influence the type of IgG subclasses expressed in the omentum of HGSOC patients. Chemotherapy enhances the expression of IgG1, IgG2 and IgG3 immunoglobulins in omentum with residual disease. This supports the notion that B cells are involved in the anti-tumor immune response in HGSOC metastases. In conclusion, our data suggest that B cells actively participate to the anti-tumor immune response in HGSOC metastases. This response is preferentially Th1 oriented through the production of cytokines and dominant expression of IgG1 immunoglobulins. Enhancing the B cell dependent anti-tumor immune response could be a potential strategy for the treatment of HGSOC patients. Iglesia MD, Vincent BG, Parker JS, Hoadley KA, Carey LA, Perou CM, Serody JS (2014) Prognostic B-cell signatures using mRNA-seq in patients with subtype-specific breast and ovarian cancer. Clin Cancer Res 20: 3818-3829 Nielsen JS, Sahota RA, Milne K, Kost SE, Nesslinger NJ, Watson PH, Nelson BH (2012) CD20+ tumor-infiltrating lymphocytes have an atypical CD27- memory phenotype and together with CD8+ T cells promote favorable prognosis in ovarian cancer. Clin Cancer Res 18: 3281-3292 Citation Format: Anne Montfort, Steffen Boehm, Thomas Dowe, Joanne Topping, Michelle Lockley, Melania Capasso, Frances Balkwill. B cells actively participate to the anti-cancer immune response in high grade serous ovarian cancer metastases. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 455. doi:10.1158/1538-7445.AM2015-455