Human ovarian carcinoma cells generate CD4+CD25+ regulatory T cells from peripheral CD4+CD25− T cells through secreting TGF-β

Li, Xiao; Ye, Feng; Chen, Huaizeng; Lü, Weiguo; Wan, Xiaoxia; Xie, Xing

doi:10.1016/j.canlet.2007.01.024

Cited by 45 publications

(34 citation statements)

References 24 publications

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“…Together, these results show that Panc89 cells inhibit, in a Foxp3-dependent manner, the proliferation of naive T cells without generally impeding their activation. Recent reports have shown that tumor cells can induce Treg via secretion of TGF-h (22,28,39). Blocking TGF-h in the coculture with anti-TGF-h2 antibody did not reverse the antiproliferative effect on the T cells (data not shown).…”

Section: Resultsmentioning

confidence: 77%

Foxp3 Expression in Pancreatic Carcinoma Cells as a Novel Mechanism of Immune Evasion in Cancer

Hinz¹,

et al. 2007

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The forkhead transcription factor Foxp3 is highly expressed in CD4+CD25+ regulatory T cells (Treg) and was recently identified as a key player in mediating their inhibitory functions. Here, we describe for the first time the expression and function of Foxp3 in pancreatic ductal adenocarcinoma cells and tumors. Foxp3 expression was induced by transforming growth factor-B2 (TGF-B2), but not TGF-B1 stimulation in these cells, and was partially suppressed following antibody-mediated neutralization of TGF-B2. The TGF-B2 effect could be mimicked by ectopic expression of a constitutively active TGF-B type I receptor/ALK5 mutant. Down-regulation of Foxp3 with small interfering RNA (siRNA) in pancreatic carcinoma cells resulted in the up-regulation of interleukin 6 (IL-6) and IL-8 expression, providing evidence for a negative transcriptional activity of Foxp3 also in these epithelial cells. Coculture of Foxp3-expressing tumor cells with naive T cells completely inhibited T-cell proliferation, but not activation, and this antiproliferative effect was partially abrogated following specific inhibition of Foxp3 expression. These findings indicate that pancreatic carcinoma cells share growth-suppressive effects with Treg and suggest that mimicking Treg function may represent a new mechanism of immune evasion in pancreatic cancer. [Cancer Res 2007;67(17):8344-50]

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Section: Resultsmentioning

confidence: 77%

Foxp3 Expression in Pancreatic Carcinoma Cells as a Novel Mechanism of Immune Evasion in Cancer

Hinz¹,

et al. 2007

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“…[33] Thus we tested the effect of cancer associated fibroblast inducing factors on fibroblast proliferation in our system. [34] We found that TGF 1β but not TNF 1α, increased fibroblast proliferation ( Figure S1, Supporting Information). We also observed fibroblasts in the coculture assay to access whether they were also affected by cancer cells.…”

Section: Angiogenesismentioning

confidence: 83%

“…The results seem reasonable because those factors have been thought to be upregulated in vivo in the TME via the activation of macrophages and other immune cells. [34,35] However we confined this study to the tumor fibroblast interaction and compensated for the immune cell derived factors with extrinsic factors in the following experi ments, to limit the complexity of our model system.…”

Section: Angiogenesismentioning

confidence: 99%

Biomimetic Model of Tumor Microenvironment on Microfluidic Platform

Chung

Ahn

Son

et al. 2017

Adv Healthcare Materials

114

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COMMUNICATION (1 of 7)© 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim Biomimetic Model of Tumor Microenvironment on Microfluidic PlatformMinhwan Chung, Jungho Ahn, Kyungmin Son, Sudong Kim, and Noo Li Jeon* DOI: 10.1002/adhm.201700196 "cure." [4,5] The TME is a complex, inter acting system including the tumor itself, other noncancerous cell types such as immune, stromal and endothelial cells, and the extracellular matrix surrounding these cells. [6,7] This complexity has largely prevented a comprehensive understanding of TME in conventional in vitro models, which have been too simple to recapitulate the intricate interactions ( Figure 1A). [8,9] During recent decades, microfabrication technologies have been shown to be valu able tools in the exploration of tumor pro gression. Recently, several studies using microfluidic platform have been reported that recreate the 3D context of each aspect of the TME and metastasis in vitro. [10][11][12][13] However, to our knowledge, no versatile in vitro experimental model that reconstitutes direct interplay between constituents of the TME during tumorigenesis has yet been reported. Here we describe a biomimetic TME model to mimic the complex inter actions of the tumor, stromal, and endothe lial cells, all of which are essential components of the TME that hinder the effective treatment of cancers. [14][15][16] We used a micro fluidic platform from our previous studies. [17,18] Various effects of extracellular matrix (ECM) and the stroma on the physiology of tumor cells and angiogenesis were tested. Finally, we could mimic simultaneous angiogenesis and lymphangiogenesis in the TME with interactions between the tumor cells.Although the cancer stroma is well known for its many roles in multiple cancer stages, direct interactions between cancer and stromal cells have remained largely unknown. [19] Addition ally, cancer cell interaction with the ECM is another TME factor that regulates the behavior of the cancer cells and their resist ance to drugs. [20] Recently, in vitro activation of tumor stoma and corresponding ECM remodeling have been reported using a microfluidic platform. [21] However, single cell responses of the cancer cells in response to the stroma coculture and ECM composition has not yet been described. To examine cancer stromal cell interaction with a 3D ECM, we used a micro fluidic 3D cell culture platform previously reported from our group. [17,18] The array of microposts in the platform enabled straightforward micropatterning of the hydrogel which allowed flexible experimental configurations. We first cocultured cancer and stromal cells within fibrin gel in different microchannels, which still allowed the cells to interact with each other in a par acrine manner ( Figure 1B). Twice as many fibroblasts as cancer cells were patterned to exclude an autocrine or indirect effectThe "Tumor microenvironment" (TME) is a complex, interacting system of the tumor and its surrounding environment. The TME has drawn more attention recently in attempts to overcome current drug...

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“…Indeed, several studies have shown that tumor-derived TGF-β played an important role in the generation of T reg cells in the tumor microenvironment [62,63] . In addition, our group has found that CD70-expressing lymphoma B cells induced Foxp3 expression in intratumoral CD4 + CD25 -T cells and interaction between CD27-CD70 was involved in lymphoma B cell-mediated generation of T reg cells [16] .…”

Section: Cd25mentioning

confidence: 99%

The Role of Treg Cells in the Cancer Immunological Response

Yang

Ansell

2009

American J. of Immunology

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Problem statement: T cell-mediated immunosuppression has been observed for decades without clarification as to which factor was responsible for this observation. The identification of CD4 + CD25 + regulatory T (T reg ) cells represents a milestone in the filed of immunology and provides an explanation for T-cell-mediated immunosuppression. Although T reg cells were originally identified for their ability to prevent organ-specific autoimmune disease in mice, emerging evidence suggests that T reg cells play a pivotal role in tumor immunity and contribute to tumor growth and progression, thereby having an important impact on the outcome of cancer patients. Approach: This article reviewed the medical literature to describe how T reg cells affect anti-tumor immunity. Results: T reg cells suppressed anti-tumor immunity by inhibiting the effector functions of tumor-specific T cells and NK cells. Importantly, tumor cells played an active role in recruiting and generating T reg cells and creating a suppressive tumor microenvironment. Strategies to deplete T reg cells or inhibit their function had yielded promising results by enhancing anti-tumor immunity in experimental studies as well as clinical practice. Conclusion: A better understanding of the pathophysiology of T reg cells not only increased our knowledge in a variety of aspects of immunology but also potentially benefited cancer patients.

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Human ovarian carcinoma cells generate CD4+CD25+ regulatory T cells from peripheral CD4+CD25− T cells through secreting TGF-β

Cited by 45 publications

References 24 publications

Foxp3 Expression in Pancreatic Carcinoma Cells as a Novel Mechanism of Immune Evasion in Cancer

Foxp3 Expression in Pancreatic Carcinoma Cells as a Novel Mechanism of Immune Evasion in Cancer

Biomimetic Model of Tumor Microenvironment on Microfluidic Platform

The Role of Treg Cells in the Cancer Immunological Response

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