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 B�hm, 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., B�hm, 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; B�hm, 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, B�hm, 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 A, Pearce O, Maniati E, Vincent BG, Bixby L, B�hm S et al. A strong B-cell response is part of the immune landscape in human high-grade serous ovarian metastases. Clinical Cancer Research. 2017 Jan 1;23(1):250-262. Available from, DOI: 10.1158/1078-0432.CCR-16-0081
Montfort, Anne ; Pearce, Oliver ; Maniati, Eleni ; Vincent, Benjamin G. ; Bixby, Lisa ; B�hm, 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 - B�hm,Steffen

AU - Dowe,Thomas

AU - Wilkes,Edmund H.

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AU - Thompson,Richard

AU - Topping,Joanne

AU - Cutillas,Pedro R.

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AU - Serody,Jonathan S.

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