Antitumor effector B cells directly kill tumor cells via the Fas/FasL pathway and are regulated by IL‐10

Abstract

We have previously reported that adoptive transfer of tumor-draining lymph node (TDLN) B cells confers tumor regression in a spontaneous pulmonary metastasis mouse model of breast cancer. In this study, we identified IL-10-producing cells within these B cells, and found that IL-10 removal, either by using IL-10−/− TDLN B cells or by systemic neutralization of IL-10, significantly augmented the therapeutic efficacy of adoptively transferred TDLN B cells. Depletion of IL-10 in B-cell adoptive transfers significantly increased cytotoxic lymphocytes (CTLs) and B-cell activity of peripheral blood mononuclear cells (PBMCs) and splenic cells in the recipient. Activated TDLN B cells express Fas ligand, which was further enhanced by co-culture of these TDLN B cells with 4T1 tumor cells. Effector B cells killed tumor cells directly in vitro in an antigen-specific and Fas ligand-dependent manner. Trafficking of TDLN B cells in vivo suggested that they were recruited to the tumor and lung as well as secondary lymphoid organs. These findings further define the biological function of antitumor effector B cells, which may offer alternative cellular therapies to cancer.

Fas-FasL expression and myocardial cell apoptosis in patients with viral myocarditis

“…Though they are meant to control the early stages of viral infection, infiltrating NK cells release perforin, which damages myocardial cells Lutz et al, 2014;Hsiao et al, 2015;Künkele et al, 2015;Peng et al, 2015). Between 7 and 14 days after the initial onset of the viral infection, most of the infiltrated cells are T-cells, which become CTLs when activated, and are programmed to kill target cells (Chen et al, 2014;Grygorczuk et al, 2015;Shi et al, 2015;Tao et al, 2015). There are two primary means by which CTLs kill target cells: one is perforin/granzyme-mediated and the other involves the Fas-FasL signaling pathway (Arai et al, 2014;Gmeiner et al, 2015;Liu et al, 2015;Nallapalle et al, 2015;O'Donnell et al, 2015;Saigusa et al, 2015).…”

Immune Contexture, Immunoscore, and Malignant Cell Molecular Subgroups for Prognostic and Theranostic Classifications of Cancers

“…The expression of surface markers' characteristic of APC by tumor-infiltrating B cells was also described in primary lung cancer (Yasuda et al, 2002) and in hepatocellular carcinoma (Shi et al, 2013). Finally, few studies suggested that some tumorinfiltrating B cells could act as true killer cells, through the expression of granzyme B and TRAIL (Shi et al, 2013), or in a Fas Ligand-dependent manner (Tao et al, 2015).…”

A new perspective: Exploring future therapeutic strategies for cancer by understanding the dual role of B lymphocytes in tumor immunity

“…Subsequently, they verified IL‐10‐producing cells among these B cells. As a result, the antitumor efficacy could be significantly enhanced with adoptive transfer of IL‐10 (‐/‐) TDLN B cells or by removal of IL‐10 from mice in which IL‐10 has been neutralized with Abs . Further evidence supports that administration of IL‐2 or adoptively transferred of TDLN B cells expressing IL‐2R could enhance this therapeutic effect …”

“…In addition to producing specific Abs, B cells are also antigen presenting cells (APCs) that are able to present foreign antigens to T cells in vivo through their surface immunoglobulins. Meanwhile, B cells have the ability to directly kill tumor cells through Fas/Fas‐ligand pathway . Moreover, the first indication that B cells may promote tumor growth came from studies that were conducted nearly 60 years ago, in which the absence of B cells impaired tumor development .…”

“…Meanwhile, B cells have the ability to directly kill tumor cells through Fas/Fas-ligand pathway. 4 Moreover, the first indication that B cells may promote tumor growth came from studies that were conducted nearly 60 years ago, in which the absence of B cells impaired tumor development. 5 Subsequently, the discovery of regulatory B cells (Bregs) may complicate the role of B cells in tumor immunity.…”