title: A Strong B-cell Response Is Part of the Immune Landscape in Human High-Grade Serous Ovarian Metastases.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
authors.affiliation: Barts Cancer Institute, Queen Mary University of London, London, UK.
authors.forename: Anne
authors.initials: A
authors.lastname: Montfort
authors.affiliation: Barts Cancer Institute, Queen Mary University of London, London, UK.
authors.forename: Oliver
authors.initials: O
authors.lastname: Pearce
authors.affiliation: Barts Cancer Institute, Queen Mary University of London, London, UK.
authors.forename: Eleni
authors.initials: E
authors.lastname: Maniati
authors.affiliation: Lineberger Comprehensive Cancer Center, Inflammatory Diseases Institute, Departments of Medicine and Microbiology and Immunology, University of North Carolina, Chapel Hill, North Carolina.
authors.forename: Benjamin G
authors.initials: BG
authors.lastname: Vincent
authors.affiliation: Lineberger Comprehensive Cancer Center, Inflammatory Diseases Institute, Departments of Medicine and Microbiology and Immunology, University of North Carolina, Chapel Hill, North Carolina.
authors.forename: Lisa
authors.initials: L
authors.lastname: Bixby
authors.affiliation: Barts Cancer Institute, Queen Mary University of London, London, UK.|Medical Oncology, Barts Health NHS Trust, London, UK.
authors.forename: Steffen
authors.initials: S
authors.lastname: Böhm
authors.affiliation: Barts Cancer Institute, Queen Mary University of London, London, UK.
authors.forename: Thomas
authors.initials: T
authors.lastname: Dowe
authors.affiliation: Barts Cancer Institute, Queen Mary University of London, London, UK.
authors.forename: Edmund H
authors.initials: EH
authors.lastname: Wilkes
authors.affiliation: Bioinformatics Core, The Francis Crick Institute, London, UK.
authors.forename: Probir
authors.initials: P
authors.lastname: Chakravarty
authors.affiliation: Barts Cancer Institute, Queen Mary University of London, London, UK.
authors.forename: Richard
authors.initials: R
authors.lastname: Thompson
authors.affiliation: Barts Cancer Institute, Queen Mary University of London, London, UK.
authors.forename: Joanne
authors.initials: J
authors.lastname: Topping
authors.affiliation: Barts Cancer Institute, Queen Mary University of London, London, UK.
authors.forename: Pedro R
authors.initials: PR
authors.lastname: Cutillas
authors.affiliation: Barts Cancer Institute, Queen Mary University of London, London, UK.|Medical Oncology, Barts Health NHS Trust, London, UK.
authors.forename: Michelle
authors.initials: M
authors.lastname: Lockley
authors.affiliation: Lineberger Comprehensive Cancer Center, Inflammatory Diseases Institute, Departments of Medicine and Microbiology and Immunology, University of North Carolina, Chapel Hill, North Carolina.
authors.forename: Jonathan S
authors.initials: JS
authors.lastname: Serody
authors.affiliation: Barts Cancer Institute, Queen Mary University of London, London, UK. f.balkwill@qmul.ac.uk m.capasso@qmul.ac.uk.
authors.forename: Melania
authors.initials: M
authors.lastname: Capasso
authors.affiliation: Barts Cancer Institute, Queen Mary University of London, London, UK. f.balkwill@qmul.ac.uk m.capasso@qmul.ac.uk.
authors.forename: Frances R
authors.initials: FR
authors.lastname: Balkwill
mesh_terms: D000917:Antibody Formation / Q000276:immunology; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D015415:Biomarkers; D045744:Cell Line, Tumor; D018284:Cystadenocarcinoma, Serous / Q000175:diagnosis* / Q000188:drug therapy / Q000276:immunology* / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007156:Immunologic Memory; D016130:Immunophenotyping; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology / Q000378:metabolism; D060787:Neoplasm Grading; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D010051:Ovarian Neoplasms / Q000175:diagnosis* / Q000188:drug therapy / Q000276:immunology* / Q000378:metabolism; D020543:Proteome; D040901:Proteomics / Q000379:methods
chemical_list: D015415:Biomarkers; D016207:Cytokines; D020543:Proteome