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

• Published in: Clinical cancer research Vol. 23; no. 1; pp. 250 - 262
• Main Authors: 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.
• Format: Journal Article
• Language: English
• Published: United States American Association for Cancer Research Inc 01.01.2017; American Association for Cancer Research
• Subjects: Adaptive immunology; Antibody Formation; Antibody Formation - immunology; Antigen (tumor-associated); Antigen-antibody complexes; Antigen-presenting cells; Antigens; Antineoplastic Combined Chemotherapy Protocols; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Antitumor activity; B-Lymphocytes; B-Lymphocytes - immunology; B-Lymphocytes - metabolism; Biomarkers; Cancer; CD20 antigen; CD8 antigen; CD86 antigen; Cell activation; Cell Line, Tumor; Chemokines; Chemotherapy; Cystadenocarcinoma, Serous; Cystadenocarcinoma, Serous - diagnosis; Cystadenocarcinoma, Serous - drug therapy; Cystadenocarcinoma, Serous - immunology; Cystadenocarcinoma, Serous - metabolism; Cytokines; Cytokines - metabolism; Cytometry; Cytotoxicity; Dendritic Cells; Dendritic Cells - immunology; Dendritic Cells - metabolism; Dendritic structure; Experimental design; Female; Flow cytometry; Gynecology and obstetrics; Human health and pathology; Humans; Immune response; Immune system; Immunohistochemistry; Immunologic Memory; Immunological memory; Immunology; Immunophenotyping; Life Sciences; Localization; Lymphocyte receptors; Lymphocytes B; Lymphocytes T; Lymphocytes, Tumor-Infiltrating; Lymphocytes, Tumor-Infiltrating - immunology; Lymphocytes, Tumor-Infiltrating - metabolism; Metastases; Metastasis; Multiplexing; Neoplasm Grading; Neoplasm Metastasis; Neoplasm Staging; Ovarian cancer; Ovarian Neoplasms; Ovarian Neoplasms - diagnosis; Ovarian Neoplasms - drug therapy; Ovarian Neoplasms - immunology; Ovarian Neoplasms - metabolism; Peritoneum; Plasma cells; Proteome; Proteomics; Proteomics - methods; Quality; Stroma; T cell receptors; Transcription
• ISSN: 1078-0432; 1557-3265; 1557-3265
• DOI: 10.1158/1078-0432.CCR-16-0081

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.