TGF-β insensitive dendritic cells: an efficient vaccine for murine prostate cancer

Wang, Fu Li; Qin, Wenzhi; Wen, Wei; Tian, Feng; Song, Bin; Zhang, Qiang; Lee, Chung; Zhong, Weide; Guo, Ying; Wang, He

doi:10.1007/s00262-007-0322-3

Cited by 20 publications

(20 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Results of our previous studies have also shown that adoptive transfer of murine-derived TGF-β-insensitive CD8 + T cells or DCs represent an efficient immunotherapeutic strategy in the treatment of murine prostate cancer (6)(7)(8)(9). In the present study, using this one-to-one adoptive transfer strategy, we further confirm that tumor-reactive TGF-β-insensitive CD8 + T cells is sufficient for tumor rejection.…”

Section: Discussionsupporting

confidence: 72%

“…Moreover, inhibition of TGF-β signaling in DC also enhanced the efficacy of DC-based vaccines (8,9). Although such TGF-β inhibition strategies are promising therapeutic approaches, little is known about its effects on human malignancies in vivo.…”

mentioning

confidence: 99%

“…Moreover, inhibition of TGF-β signaling in DC also enhanced the efficacy of 9). Although such TGF-β inhibition strategies are promising therapeutic approaches,…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Immunotherapy for Human Renal Cell Carcinoma by Adoptive Transfer of Autologous Transforming Growth Factor β–Insensitive CD8+ T Cells

Wang

Wen

Yuan

et al. 2010

Clinical Cancer Research

Self Cite

View full text Add to dashboard Cite

Purpose: Transforming growth factor-β (TGF-β) is a potent immunosuppressor that has been associated with tumor evasion from the host immune surveillance and, thus, tumor progression. We tested a novel immunotherapy for human renal cell cancer (RCC) using a technique that involves the adoptive transfer of autologous tumor-reactive, TGF-β-insensitive CD8 + T cells into human RCC-challenged immunodeficient mice to identify its potent antitumor responses.Experimental Design: The present study was conducted using a one-to-one adoptive transfer strategy to treat tumor-bearing severe combined immunodeficient (SCID/beige) mouse. The SCID/beige mice were humanized with peripheral blood mononuclear cells from patients with RCC (Hu-PBMC-SCID) before adoptive transfer. Autologous CD8 + T cells were expanded ex vivo using autologous patient's dendritic cells pulsed with the tumor lysate and rendered TGF-β insensitive by dominant-negative TGF-β type II receptor. In addition, human RCC cell lines were generated using patients' tumor cells injected into SCID/beige mice. Renal cell carcinoma (RCC) is the most common solid tumor of the kidney in adults. It has previously been reported that the overproduction of TGF-β by RCC cells may lead to tumor evasion from the host immune surveillance and subsequent tumor progression (1-4). Similarly, inhibition of transforming growth factor-βTGF-β signaling using a dominant-negative TGF-β type II receptor construct (TβRIIDN) generates an immune response capable of eradicating tumors in mice challenged with live tumor cells (5).We have previously shown that murine CD8 + T cells that are rendered insensitive to TGF-β could activate the antitumor immune response cycle in prostate cancer and subsequently eradicate lung metastases (6, 7). Moreover, inhibition of TGF-β signaling in DC also enhanced the efficacy of 9). Although such TGF-β inhibition strategies are promising therapeutic approaches,

show abstract

Section: Discussionsupporting

confidence: 72%

mentioning

confidence: 99%

See 1 more Smart Citation

Immunotherapy for Human Renal Cell Carcinoma by Adoptive Transfer of Autologous Transforming Growth Factor β–Insensitive CD8+ T Cells

Wang

Wen

Yuan

et al. 2010

Clinical Cancer Research

Self Cite

View full text Add to dashboard Cite

show abstract

“…TAK1 is the primary kinase activated by TRAF6, but TAK1ΔDC mice that lack TAK1 in the DC compartment, are not reported to develop a similar gut phenotype (Wang et al, 2007). However, TAK1ΔDC mice do exhibit a Treg cell defect.…”

Section: Discussionmentioning

confidence: 99%

Dendritic Cell Expression of the Signaling Molecule TRAF6 Is Critical for Gut Microbiota-Dependent Immune Tolerance

et al. 2013

View full text Add to dashboard Cite

SUMMARY The intracellular signaling molecule TRAF6 is critical for Toll-like receptor (TLR)-mediated activation of dendritic cells (DCs). We now report that DC-specific deletion of TRAF6 (TRAF6ΔDC) resulted, unexpectedly, in loss of mucosal tolerance, characterized by spontaneous development of T helper 2 (Th2) cells in the lamina propria, and eosinophilic enteritis and fibrosis in the small intestine. Loss of tolerance required the presence of gut commensal microbiota, but was independent of DC-expressed MyD88. Further, TRAF6ΔDC mice exhibited decreased regulatory T (Treg) cell numbers in the small intestine, and diminished induction of iTreg cells in response to model antigen. Evidence suggested this defect was associated with diminished DC expression of interleukin-2 (IL-2). Finally, we demonstrate that aberrant Th2 cell-associated responses in TRAF6ΔDC mice could be mitigated via restoration of Treg cell activity. Collectively, our findings reveal a role for TRAF6 in directing DC maintenance of intestinal immune tolerance through balanced induction of Treg versus Th2 cell immunity.

show abstract

“…Another approach aimed at manipulating TGF- β to improve antitumor immune responses involves generation of TGF- β insensitive DC vaccines. Transduced DCs, which have been rendered insensitive to TGF- β , maintain their normal phenotype, present upregulated expression of surface costimulatory molecules (CD80/CD86) and induce potent tumor-specific cytotoxic T lymphocyte responses in vivo [150]. …”

Section: Shifting the Balance: Strategies To Improve Homing And Acmentioning

confidence: 99%

From Tumor Immunosuppression to Eradication: Targeting Homing and Activity of Immune Effector Cells to Tumors

Draghiciu

Nijman

Daemen

2011

Clinical and Developmental Immunology

View full text Add to dashboard Cite

Unraveling the mechanisms used by the immune system to fight cancer development is one of the most ambitious undertakings in immunology. Detailed knowledge regarding the mechanisms of induction of tolerance and immunosuppression within the tumor microenvironment will contribute to the development of highly effective tumor eradication strategies. Research within the last few decades has shed more light on the matter. This paper aims to give an overview on the current knowledge of the main tolerance and immunosuppression mechanisms elicited within the tumor microenvironment, with the focus on development of effective immunotherapeutic strategies to improve homing and activity of immune effector cells to tumors.

show abstract

TGF-β insensitive dendritic cells: an efficient vaccine for murine prostate cancer

Cited by 20 publications

References 36 publications

Immunotherapy for Human Renal Cell Carcinoma by Adoptive Transfer of Autologous Transforming Growth Factor β–Insensitive CD8+ T Cells

Immunotherapy for Human Renal Cell Carcinoma by Adoptive Transfer of Autologous Transforming Growth Factor β–Insensitive CD8+ T Cells

Dendritic Cell Expression of the Signaling Molecule TRAF6 Is Critical for Gut Microbiota-Dependent Immune Tolerance

From Tumor Immunosuppression to Eradication: Targeting Homing and Activity of Immune Effector Cells to Tumors

Contact Info

Product

Resources

About