A Strong B-cell Response Is Part of the Immune Landscape in Human High-Grade Serous Ovarian Metastases
- 1 January 2017
- journal article
- Published by American Association for Cancer Research (AACR) in Clinical Cancer Research
- Vol. 23 (1), 250-262
- https://doi.org/10.1158/1078-0432.ccr-16-0081
Abstract
Purpose: In high-grade serous ovarian cancer (HGSOC), higher densities of both B cells and the CD8+ T-cell infiltrate were associated with a better prognosis. However, the precise role of B cells in the antitumor response remains unknown. As peritoneal metastases are often responsible for relapse, our aim was to characterize the role of B cells in the antitumor immune response in HGSOC metastases. Experimental Design: Unmatched pre and post-chemotherapy HGSOC metastases were studied. B-cell localization was assessed by immunostaining. Their cytokines and chemokines were measured by a multiplex assay, and their phenotype was assessed by flow cytometry. Further in vitro and in vivo assays highlighted the role of B cells and plasma cell IgGs in the development of cytotoxic responses and dendritic cell activation. Results: B cells mainly infiltrated lymphoid structures in the stroma of HGSOC metastases. There was a strong B-cell memory response directed at a restricted repertoire of antigens and production of tumor-specific IgGs by plasma cells. These responses were enhanced by chemotherapy. Interestingly, transcript levels of CD20 correlated with markers of immune cytolytic responses and immune complexes with tumor-derived IgGs stimulated the expression of the costimulatory molecule CD86 on antigen-presenting cells. A positive role for B cells in the antitumor response was also supported by B-cell depletion in a syngeneic mouse model of peritoneal metastasis. Conclusions: Our data showed that B cells infiltrating HGSOC omental metastases support the development of an antitumor response. Clin Cancer Res; 23(1); 250–62. ©2016 AACR.Keywords
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Funding Information
- Cancer Research UK (A16354)
- Swiss Cancer League (BIL KLS2883-02-2012)
- European Research Council (ERC322566)
- Barts and The London Charity (467/1307, BLT 297/2249)
- Bloodwise (ref 12002)
- UNC (5K12CA120780)
- NCI (P50 CA058223)
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