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

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.

Tumor-infiltrating B cells signal functional humoral immune responses in breast cancer

“…Detailed characterization of TIL-B in 9 ovarian tumors found an overwhelming majority of IgD -CD38 /lo TIL-B, indicative of a memory B cell phenotype; however, these TIL-B were all CD27 -(57). These atypical memory B cells have also been reported in ovarian metastases, in association with memory B cells with a more classical phenotype (59). In chronic infections characterized by an inability to eradicate the pathogen, B cells with an atypical memory phenotype have been shown to accumulate in patients (60).…”

Context-dependent roles of complement in cancer

“…C1q can bind over 100 different targets, but the major ones are the IgG and IgM-containing immune complexes 2 . Indeed, IgM and IgG antibodies have been detected in several tumor types such as in NSCLC 91 , ovarian 92,93 , KIRC 21 and breast 94 cancers. These antibodies may come from the circulation or be produced at the tumor site 91,93 potentially initiating the complement cascade.…”

Tumor-associated tertiary lymphoid structure predicts postoperative outcomes in patients with primary gastrointestinal stromal tumors

“…35 Furthermore, PD-1 hi CD8 + T cells, PD-1 hi CD4 + T FH cells and DC-LAMP + DCs were observed in the follicular B cell zone of TLS. 40,44 This likely indicated an essential role of the TLS in promoting an interaction of T and B cells to generate an effective anti-tumor response. 40,44 Imatinib significantly improves the prognosis of GIST patients, 11 however, imatinib resistance is an inevitable consequence.…”

“…Mature dendritic cells (DCs) present antigens to CD4 + T cells to activate cellular immunity in the T cell zone, 39 while DC-LAMP + DCs in the germinal center present antigens to B cells to induce humoral immunity. 40 B cells could also present antigens to CD8 + T cells, possibly through CD80 and CD40 receptors on B cells. This replaces the need for CD4 + T cells to transmit signals to CD8 + T cells for anti-tumor responses.…”