Increased rejection of primary tumors in mice lacking B cells: Inhibition of anti-tumor CTL and TH1 cytokine responses by B cells

Sj, Shah; Divekar, Anagha; Hilchey, Shannon P.; Cho, Hyun Mi; Newman, Corliss L.; Shin, Seung Uon; Nechustan, Hovav; Challita-Eid, Pia M.; Segal, Benjamin M.; Yi, Kyung Hee; Rosenblatt, Joseph D.

doi:10.1002/ijc.21177

Cited by 203 publications

(160 citation statements)

References 39 publications

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“…Several recent investigations in mouse cancer models have revealed the existence of protumorigenic regulatory B cells (Breg; refs. [16][17][18]. Here, we identifi ed a novel protumorigenic PD-1 hi B-cell subset in human hepatocellular carcinoma (HCC).…”

Section: Introductionmentioning

confidence: 99%

PD-1hi Identifies a Novel Regulatory B-cell Population in Human Hepatoma That Promotes Disease Progression

et al. 2016

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B cells often constitute abundant cellular components in human tumors. Regulatory B cells that are functionally defi ned by their ability to produce IL10 downregulate infl ammation and control T-cell immunity. Here, we identifi ed a protumorigenic subset of B cells that constitutively expressed higher levels of programmed cell death-1 (PD-1) and constituted ∼ 10% of all B cells in advanced-stage hepatocellular carcinoma (HCC).

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Section: Introductionmentioning

confidence: 99%

PD-1hi Identifies a Novel Regulatory B-cell Population in Human Hepatoma That Promotes Disease Progression

et al. 2016

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“…A variety of murine tumors are either completely rejected or demonstrated reduced growth in the absence of B cells, including the EL-4 thymoma, MC38 colon carcinoma and the EMT-6 breast carcinoma, D5 mouse melanoma (5)(6)(7)(8). These tumors show reduced growth or are rejected in B-celldeficient mice (BCDM), and growth is restored following reconstitution with adoptively transferred B cells (5,7). Reconstitution with B cells is associated with a reduction in CD8 + T-cell and NK-cell infiltration, and reduced anti-tumor immune response (7).…”

Section: Introductionmentioning

confidence: 99%

“…Reconstitution with B cells is associated with a reduction in CD8 + T-cell and NK-cell infiltration, and reduced anti-tumor immune response (7). Studies involving BCR-transgenic mice or adoptive transfer of B cells from MHC-II −/− mice into BCDM indicate that B cells may mediate these effects through antigen non-specific mechanisms (5,9). B cells can also promote expansion of Tregs within the tumor bed, and antibody depletion of CD25 + T cells restores anti-tumor response (7).…”

Section: Introductionmentioning

confidence: 99%

Mammary-tumor-educated B cells acquire LAP/TGF-β and PD-L1 expression and suppress anti-tumor immune responses

Zhang

Morgan

Chen

et al. 2016

International Immunology

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“…Therefore, novel studies focusing on the role of B cells as negative modulators of the antitumor response are currently underway. Evidence that accounts for the role of B cells in tumor-induced immunosuppression includes the existence of human B cells with a regulatory phenotype in solid tumors (11), the B cell-mediated induction of Tregs expansion (12)(13)(14) and the increase of tumor growth (12,(15)(16)(17). Methylcolanthrene-induced murine fibrosarcoma (MCC) is a highly immunogenic tumor that elicits an early specific antitumor immune reaction, which is not strong enough to impede tumor growth (18)(19)(20)(21).…”

Section: Introductionmentioning

confidence: 99%

B cells inhibit the antitumor immunity against an established murine fibrosarcoma

et al. 2017

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Abstract. Despite the classic role of B cells in favoring the immune response, an inhibitory action of B lymphocytes in tumor immunity has emerged in certain studies. In methylcolanthrene-induced murine fibrosarcoma (MCC), the loss of immunogenicity and the establishment of tolerance are paralleled by systemic immune suppression and the appearance of B + IL-10 + cells in tumor-draining lymph nodes. The present study aimed to assess the role of the B + IL-10 + cell population in the immune evasion and tolerance induced by MCC through the depletion of B cells in mice at various times of tumor progression: Prior to or subsequent to tumor implantation. Tumor growth and immunological parameters were evaluated. B cell depletion prior to tumor inoculum enhanced tumor growth, initiating the onset of the tumor-induced systemic immune response; however, an increase in the T regulatory cells (Tregs) at the tumor-draining lymph node could account for tumor exacerbation. B cell depletion once the tumor was established resulted in decreased tumor growth and a delayed onset of tolerance. Additionally, B cell absence exacerbated T cell dependent-tumor rejection, reduced Tregs and increased cytotoxic CD8 + T cells. In vitro analysis showed a direct effect of B cells upon T cell proliferation.In conclusion, B cell depletion exerts opposite effects when performed prior to or subsequent to tumor implantation. In this initially immunogenic tumor, B cell absence would delay the establishment of immunological tolerance probably by unmasking a pre-existing antitumor response. The present findings elucidate the convenience of modulating B cells in the development of future and more effective immunotherapies against cancer. IntroductionThe role of the host immune system in the control of cancer progression has been assessed for several years; at present, it is vastly accepted that antitumor immunity occurs and that numerous tumors have developed mechanisms to escape immune control, leading to malignant progression (1). The mechanisms responsible for antitumor immunity failure in individuals with cancer include a wide diversity of soluble immunosuppressive factors, including transforming growth factor β (TGFβ), interleukin 10 (IL-10), reactive oxygen species (ROS), enzymes and inhibitory ligands such as Fas ligand (FasL) or TNF-related apoptosis-inducing ligand, released by tumor cells or by other regulatory cells in the tumor microenvironment (2). The majority of immunotherapies against cancer aim to counteract the action of regulatory cells in order to achieve tumor remission or prevent recurrences; of these, T regulatory cells (Tregs) have been the major focus of efforts to therapeutically modulate their inhibitory activity (3,4

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Increased rejection of primary tumors in mice lacking B cells: Inhibition of anti-tumor CTL and TH1 cytokine responses by B cells

Cited by 203 publications

References 39 publications

PD-1hi Identifies a Novel Regulatory B-cell Population in Human Hepatoma That Promotes Disease Progression

PD-1hi Identifies a Novel Regulatory B-cell Population in Human Hepatoma That Promotes Disease Progression

Mammary-tumor-educated B cells acquire LAP/TGF-β and PD-L1 expression and suppress anti-tumor immune responses

B cells inhibit the antitumor immunity against an established murine fibrosarcoma

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