A strong B-cell response is part of the immune landscape in human high-grade serous ovarian metastases

Anne Montfort, Oliver Pearce, Eleni Maniati, Benjamin G. Vincent, Lisa Bixby, Steffen Böhm, Thomas Dowe, Edmund H. Wilkes, Probir Chakravarty, Richard Thompson, Joanne Topping, Pedro R. Cutillas, Michelle Lockley, Jonathan S. Serody, Melania Capasso, Frances R. Balkwill

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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.

LanguageEnglish (US)
Pages250-262
Number of pages13
JournalClinical Cancer Research
Volume23
Issue number1
DOIs
StatePublished - Jan 1 2017

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B-Lymphocytes
Neoplasm Metastasis
Ovarian Neoplasms
Plasma Cells
CD86 Antigens
Drug Therapy
Neoplasm Antigens
Antigen-Presenting Cells
Antigen-Antibody Complex
Chemokines
Dendritic Cells
Flow Cytometry
Research Design
Biomarkers
Cytokines
T-Lymphocytes
Phenotype
Recurrence
Neoplasms

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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Montfort, A., Pearce, O., Maniati, E., Vincent, B. G., Bixby, L., Böhm, S., ... Balkwill, F. R. (2017). A strong B-cell response is part of the immune landscape in human high-grade serous ovarian metastases. Clinical Cancer Research, 23(1), 250-262. DOI: 10.1158/1078-0432.CCR-16-0081

A strong B-cell response is part of the immune landscape in human high-grade serous ovarian metastases. / Montfort, Anne; Pearce, Oliver; Maniati, Eleni; Vincent, Benjamin G.; Bixby, Lisa; Böhm, Steffen; Dowe, Thomas; Wilkes, Edmund H.; Chakravarty, Probir; Thompson, Richard; Topping, Joanne; Cutillas, Pedro R.; Lockley, Michelle; Serody, Jonathan S.; Capasso, Melania; Balkwill, Frances R.

In: Clinical Cancer Research, Vol. 23, No. 1, 01.01.2017, p. 250-262.

Research output: Contribution to journalArticle

Montfort, A, Pearce, O, Maniati, E, Vincent, BG, Bixby, L, Böhm, S, Dowe, T, Wilkes, EH, Chakravarty, P, Thompson, R, Topping, J, Cutillas, PR, Lockley, M, Serody, JS, Capasso, M & Balkwill, FR 2017, 'A strong B-cell response is part of the immune landscape in human high-grade serous ovarian metastases' Clinical Cancer Research, vol. 23, no. 1, pp. 250-262. DOI: 10.1158/1078-0432.CCR-16-0081
Montfort, Anne ; Pearce, Oliver ; Maniati, Eleni ; Vincent, Benjamin G. ; Bixby, Lisa ; Böhm, Steffen ; Dowe, Thomas ; Wilkes, Edmund H. ; Chakravarty, Probir ; Thompson, Richard ; Topping, Joanne ; Cutillas, Pedro R. ; Lockley, Michelle ; Serody, Jonathan S. ; Capasso, Melania ; Balkwill, Frances R./ A strong B-cell response is part of the immune landscape in human high-grade serous ovarian metastases. In: Clinical Cancer Research. 2017 ; Vol. 23, No. 1. pp. 250-262
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AU - Bixby,Lisa

AU - Böhm,Steffen

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AU - Thompson,Richard

AU - Topping,Joanne

AU - Cutillas,Pedro R.

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AU - Serody,Jonathan S.

AU - Capasso,Melania

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