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Clin Cancer Res. 2017 Jan 1;23(1):250-262. doi: 10.1158/1078-0432.CCR-16-0081. Epub 2016 Jun 27.

A Strong B-cell Response Is Part of the Immune Landscape in Human High-Grade Serous Ovarian Metastases.

Author information

1
Barts Cancer Institute, Queen Mary University of London, London, UK.
2
Lineberger Comprehensive Cancer Center, Inflammatory Diseases Institute, Departments of Medicine and Microbiology and Immunology, University of North Carolina, Chapel Hill, North Carolina.
3
Medical Oncology, Barts Health NHS Trust, London, UK.
4
Bioinformatics Core, The Francis Crick Institute, London, UK.
5
Barts Cancer Institute, Queen Mary University of London, London, UK. f.balkwill@qmul.ac.uk m.capasso@qmul.ac.uk.

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.

PMID:
27354470
PMCID:
PMC5928522
DOI:
10.1158/1078-0432.CCR-16-0081
[Indexed for MEDLINE]
Free PMC Article

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