Breast cancer‐derived transforming growth factor‐β and tumor necrosis factor‐α compromise interferon‐α production by tumor‐associated plasmacytoid dendritic cells

Sisirak, Vanja; Vey, Nelly; Goutagny, Nadège; Renaudineau, Sarah; Malfroy, Marine; Thys, Sandra; Treilleux, Isabelle; Labidi-Galy, Sana Intidhar; Bachelot, Thomas; Dezutter‐Dambuyant, Colette; Ménétrier‐Caux, Christine; Blay, Jean‐Yves; Caux, Christophe; Bendriss‐Vermare, Nathalie

doi:10.1002/ijc.28072

Cited by 83 publications

(72 citation statements)

References 27 publications

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“…These data suggest that soluble factors secreted by tumor cells may be partly responsible for inducing BST-2 expression in mammary epithelial cells. Moreover, our data is in agreement with a published report which showed that breast tumor environment blocks type IFN production (Sisirak et al, 2013). To identify the soluble factors present in TCM, we used mouse inflammatory cytokines multi-analyte ELISArray Kit to identify the cytokines secreted into culture medium.…”

Section: Resultssupporting

confidence: 94%

BST-2/tetherin is overexpressed in mammary gland and tumor tissues in MMTV-induced mammary cancer

et al. 2013

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BST-2 restricts MMTV replication, but once infection has established, MMTV modulates BST-2 levels. MMTV-directed BST-2 modulation is tissue-specific and dependent on infection and neoplastic transformation status of cells. In the lymphoid compartment of infected mice, BST-2 expression is first upregulated and then significantly downregulated regardless of absence or presence of mammary tumors. However, in mammary gland tissues, upregulation of BST-2 expression is dependent on the presence of mammary tumors and tumor tissues themselves have high BST-2 levels. Elevated BST-2 expression in these tissues is not attributable to IFN since levels of IFNα and IFNγ negatively correlate with BST-2. Importantly, soluble factors released by tumor cells suppress IFNα and IFNγ but induce BST-2. These data suggest that overexpression of BST-2 in carcinoma tissues could not be attributed to IFNs but to a yet to be determined factor that upregulates BST-2 once oncogenesis is initiated.

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Section: Resultssupporting

confidence: 94%

BST-2/tetherin is overexpressed in mammary gland and tumor tissues in MMTV-induced mammary cancer

et al. 2013

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“…These data are consistent with the specific alteration of TLR9 response previously reported by us (19,20) and others on both human tumor and immune cells (17,28). Although pDC hyporesponsiveness to TLR9 ligands might be explained by receptor downregulation (17,28), we showed that it is rather due to a specific interference of the tumor microenvironment, for instance via IRF7 downregulation (29). Tumor-induced TLR9 loss of function might represent an immunosubversion mechanism to avoid immune alert by putative endogenous ligands for TLR9 within the tumor microenvironment, such as described in autoimmune disorders (30)(31)(32).…”

Section: Discussionsupporting

confidence: 93%

Tumor Promotion by Intratumoral Plasmacytoid Dendritic Cells Is Reversed by TLR7 Ligand Treatment

et al. 2013

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Plasmacytoid dendritic cells (pDC) are key regulators of antiviral immunity. In previous studies, we reported that pDC-infiltrating human primary breast tumors represent an independent prognostic factor associated with poor outcome. To understand this negative impact of tumor-associated pDC (TApDC), we developed an orthotopic murine mammary tumor model that closely mimics the human pathology, including pDC and regulatory T cell (Treg) infiltration. We showed that TApDC are mostly immature and maintain their ability to internalize antigens in vivo and to activate CD4 þ T cells. Most importantly, TApDC were specifically altered for cytokine production in response to Toll-like receptor (TLR)-9 ligands in vitro while preserving unaltered response to TLR7 ligands (TLR7L). In vivo pDC depletion delayed tumor growth, showing that TApDC provide an immunesubversive environment, most likely through Treg activation, thus favoring tumor progression. However, in vivo intratumoral administration of TLR7L led to TApDC activation and displayed a potent curative effect. Depletion of pDC and type I IFN neutralization prevented TLR7L antitumoral effect. Our results establish a direct contribution of TApDC to primary breast tumor progression and rationalize the application of TLR7 ligands to restore TApDC activation in breast cancer. Cancer Res; 73(15); 4629-40. Ó2013 AACR.

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“…Certain studies have reported that targeting tumor-associated plasmacytoid dendritic cells to restore their IFN-α production may be an achievable therapeutic strategy to induce antitumor immunity in breast cancer (30)(31)(32). These studies suggested that IFN-α was important for the inhibition of breast cancer development (30)(31)(32). In the present study, the level of IFN-α in all six groups treated with RJ was significantly increased, indicating that RJ serves an important role in immunomodulation.…”

Section: Discussionsupporting

confidence: 61%

Section: Discussionmentioning

confidence: 99%

The effect of royal jelly on the growth of breast cancer in mice

et al. 2017

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Abstract. Due to various pharmacological properties, including antioxidative, anti-inflammatory and antibiotic properties, royal jelly (RJ) has been widely consumed in daily diets in numerous countries. In the present study, the effect of RJ on 4T1-bearing mice was investigated. The study was performed by feeding 4T1-bearing mice with RJ using either the prophylactic-therapeutic (PTRJ) or therapeutic (TRJ) method. The experimental results for the PTRJ group demonstrated that the weight of tumor was significantly reduced (RJ 0.5 and 1.5 g/kg); and in the serum, the levels of interleukin (IL)-2 (RJ 0.5 and 1.5 g/kg), interferon (IFN)-α, superoxide dismutase (SOD) and total antioxidant capacity (T-AOC) were significantly elevated, but the concentrations of IL-4 (RJ 0.5 and 1.5 g/kg) and IL-10 (RJ 1.0 g/kg) were significantly decreased. In addition, the activities of T-AOC and glutathione reductase (GR) were significantly improved in the liver, whereas in the kidney, the activities of T-AOC and GR were significantly increased only under the dose of 0.5 g/kg. For the TRJ group, the antitumor effect of RJ was not significant; the change in IL-2, IFN-α, SOD and T-AOC levels in the serum, and the change in T-AOC and GR in liver were similar to those observed in the PTRJ groups. RJ treatment was demonstrated to reduce the development of breast tumor in mice, and simultaneously improve the antioxidant capacity of the serum, liver and kidney, particularly using the prophylactic-therapeutic method. These results corroborated the efficacy of RJ supplementation in diets. The results of the present study suggest that the antioxidant and immunomodulatory activities of RJ serve an important role on antitumor growth.

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Breast cancer‐derived transforming growth factor‐β and tumor necrosis factor‐α compromise interferon‐α production by tumor‐associated plasmacytoid dendritic cells

Cited by 83 publications

References 27 publications

BST-2/tetherin is overexpressed in mammary gland and tumor tissues in MMTV-induced mammary cancer

BST-2/tetherin is overexpressed in mammary gland and tumor tissues in MMTV-induced mammary cancer

Tumor Promotion by Intratumoral Plasmacytoid Dendritic Cells Is Reversed by TLR7 Ligand Treatment

The effect of royal jelly on the growth of breast cancer in mice

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