Therapeutic blockade of Foxp3 in experimental breast cancer models

Ayala, Mariela A. Moreno; Gottardo, María Florencia; Imsen, Mercedes; Asad, Antonela Sofía; Joffé, Elisa Bal de Kier; Casares, Noëlia; Lasarte, Juan José; Seilicovich, Adriana

doi:10.1007/s10549-017-4414-2

Cited by 29 publications

(45 citation statements)

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“…Tan et al ( 51 ) suggested that overexpression of foxp3 in tumor cells inhibited tumor growth and promoted cell apoptosis. Studies also obtained similar results in glioma ( 52 ), gastric cancer ( 53 ), breast cancer ( 54 ) and other associated tumors ( 55 ). It was reported that endogenous foxp3 overexpression inhibited gastric cancer cell proliferation and facilitated apoptosis by upregulating microRNA-146a/b and negatively regulating the NF-κB signaling pathway ( 56 ).…”

Section: Discussionsupporting

confidence: 56%

The effect of foxp3-overexpressing Treg cells on non-small cell lung cancer cells

Peng

Xue

et al. 2018

Mol Med Report

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The aim of the present study was to investigate the novel mechanisms of forkhead box protein P3 (foxp3) in T regulatory (Treg) cells in lung cancer behavior. Treg cells were isolated from the peripheral blood of healthy volunteers and then co-cultured with 95D cells. A plasmid overexpressing foxp3 was constructed and transfected into Treg cells and an MTS assay was performed to assess cell viability. Flow cytometry was performed to evaluate cell apoptosis and reverse transcription-quantitative polymerase chain reaction was used to measure mRNA expression. A Transwell assay was used to assess cell invasion. Treg cells were successfully isolated from peripheral blood with purity of 94.26%. Foxp3 expression in Treg cells was significantly increased following co-culture with 95D cells, while matrix metalloproteinase-9 expression was upregulated in 95D cells co-cultured with Treg cells. The apoptosis, invasion and migration abilities of 95D cells were suppressed by co-culture with Treg cells, whereas the adhesive ability was enhanced. Foxp3 overexpression in Treg cells enhanced the viability and invasiveness of 95D cells, whereas cell adhesion and migration were decreased. The results of the present study demonstrate that the viability and invasiveness of 95D cells are enhanced by foxp3 overexpression in Treg cells, indicating that increased levels of foxp3 in the tumor microenvironment may promote tumor cell growth.

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Section: Discussionsupporting

confidence: 56%

The effect of foxp3-overexpressing Treg cells on non-small cell lung cancer cells

Peng

Xue

et al. 2018

Mol Med Report

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“…Human GBM cells were incubated with 100 ng/ml ovine PRL or 2.5 µg/ml PRLR-A for 6 h. Then, cells were incubated with 10 µM BrdU labelling solution for the last 1.5 h and BrdU incorporation into cellular DNA strands was assessed by ELISA following manufacturer’s instructions (Roche Molecular Biochemicals, Mannheim, Germany; Cat# 11647229001) as previously described 74 . Absorbance was measured in 96-well plate spectrophotometer (Bio-Rad, Model 550) at 450 nm.…”

Section: Methodsmentioning

confidence: 99%

“…Cell viability was analysed using 3-(4,5-dimethylthiazol-2-yl)−2,5-diphenyltetrazolium bromide (MTT; Molecular Probes, Invitrogen) as described before 74 . Absorbance was determined using a 96-well plate spectrophotometer (Bio-Rad, Model 550) at 595 nm.…”

Section: Methodsmentioning

confidence: 99%

Prolactin and its receptor as therapeutic targets in glioblastoma multiforme

Asad

Candia

González

et al. 2019

Sci Rep

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Although prolactin (PRL) and its receptor (PRLR) have been detected in glioblastoma multiforme (GBM), their role in its pathogenesis remains unclear. Our aim was to explore their contribution in GBM pathogenesis. We detected PRL and PRLR in all GBM cell lines tested. PRLR activation or overexpression using plasmid transfection increased proliferation, viability, clonogenicity, chemoresistance and matrix metalloproteinase activity in GBM cells, while PRLR antagonist ∆1–9-G129R-hPRL reduced their proliferation, viability, chemoresistance and migration. Meta-analysis of transcriptomic data indicated that PRLR was expressed in all grade II-III glioma (GII-III) and GBM samples. PRL was upregulated in GBM biopsies when compared to GII-III. While in the general population tumour PRL/PRLR expression did not correlate with patient survival, biological sex-stratified analyses revealed that male patients with PRL+/PRLRHIGH GBM performed worse than PRL+/PRLRLOW GBM. In contrast, all male PRL+/PRLRHIGH GII-III patients were alive whereas only 30% of PRL+/PRLRLOW GII-III patients survived after 100 months. Our study suggests that PRLR may be involved in GBM pathogenesis and could constitute a therapeutic target for its treatment. Our findings also support the notion that sexual dimorphism should be taken into account to improve the care of GBM patients.

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“…It has been proposed that this is due to the expansion of immunosuppressive cells such as Treg cells. In an experimental study by Ayala et al [20], FOXP3 blockade improved the efficacy of dendritic cell vaccines by inhibiting Treg cells and the direct antitumour effect. It was thus proposed that FOXP3 blockade can neutralise the immunosuppressive tumour microenvironment and switch the antitumour immune response [20].…”

Section: Discussionmentioning

confidence: 99%

Analysis of Treg cell population in patients with breast cancer with respect to progesterone receptor status

Dziobek¹,

Biedka²,

Nowikiewicz³

et al. 2018

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Breast cancer is the most frequently diagnosed type of cancer in women worldwide. Both the development and progression of breast cancer are related to tumour evasion of the immune system through a process called cancer immune-editing, in which regulatory lymphocytes play an important role. The infiltration of Treg cells in patients with breast cancer has been proposed as an independent unfavourable prognostic factor. In the present study, we aimed to evaluate the percentages of the Treg cell populations in the peripheral blood of patients with breast cancer with respect to progesterone receptor expression.Peripheral blood samples were collected from 27 patients with breast cancer treated in the Clinical Department of Breast Cancer and Reconstructive Surgery of the Professor Franciszek Lukaszczyk Oncological Centre, Bydgoszcz. Flow cytometry was used to evaluate the percentage of CD25+/FOXP3+/CD127 (–/low) T cells within CD3+/CD4+ T cells.The presence of CD25+/FOXP3+/CD127 (–/low) T cells within CD3+/CD4+ T cells was identified in all the examined blood samples. A statistically significantly higher percentage of CD25+/FOXP3+/CD127 (–/low) T cells within CD3+/CD4+ T cells was observed in progesterone receptor (PR)-negative breast cancer patients when compared to PR-positive breast cancer patients.The observed high percentage of CD25+/FOXP3+/CD127 (–/low) T cells within CD3+/CD4+ T cells in PR (–) breast cancer patients when compared to PR (+) breast cancer patients seems to confirm the unfavourable prognostic significance of these cells in breast cancer patients. This may indicate a rationale for combining standard oncological treatment in breast cancer patients with Treg-depleting therapy.

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Therapeutic blockade of Foxp3 in experimental breast cancer models

Abstract: Our results suggest that Foxp3 blockade improves the therapeutic efficacy of DC vaccines by inhibition of Tregs and through a direct antitumor effect. This strategy could prove useful to neutralize the immunosuppressive microenvironment and to boost antitumor immunity in breast cancer.

Cited by 29 publications

References 50 publications

The effect of foxp3-overexpressing Treg cells on non-small cell lung cancer cells

The effect of foxp3-overexpressing Treg cells on non-small cell lung cancer cells

Prolactin and its receptor as therapeutic targets in glioblastoma multiforme

Analysis of Treg cell population in patients with breast cancer with respect to progesterone receptor status

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