Dendritic cell based antitumor vaccination: impact of functional indoleamine 2,3-dioxygenase expression

Wobser, Marion; Voigt, Heike; Houben, Roland; Eggert, Andreas O.; Freiwald, Matthias; Kaemmerer, Ulrike; Kaempgen, Eckhart; Schrama, David; Becker, Juergen C.

doi:10.1007/s00262-006-0256-1

Cited by 65 publications

(57 citation statements)

References 33 publications

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“…Our data show that activated T cells can induce IDO expression in tumor cells and negatively impact the immune response. In melanoma, it has been demonstrated that IDO can affect DC-based vaccines given that IDO-positive cells were detected by immunohistochemistry in tumor biopsies 24 h after the administration of a DC-based vaccine (48). Furthermore, IDO expression led to increased expression of FoxP3, and thus possibly T regulatory T (Treg) cells (48).…”

Section: Discussionmentioning

confidence: 99%

“…In melanoma, it has been demonstrated that IDO can affect DC-based vaccines given that IDO-positive cells were detected by immunohistochemistry in tumor biopsies 24 h after the administration of a DC-based vaccine (48). Furthermore, IDO expression led to increased expression of FoxP3, and thus possibly T regulatory T (Treg) cells (48). The complementarities between these two immunosuppressive mechanisms have been demonstrated recently by Munn and colleagues (49) as they showed that IDO-expressing plasmacytoid DC can activate resting Treg in mice.…”

Section: Discussionmentioning

confidence: 99%

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Human Activated T Lymphocytes Modulate IDO Expression in Tumors through Th1/Th2 Balance

Godin-Ethier

Pelletier

Hanafi

et al. 2009

The Journal of Immunology

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Previous cancer vaccination approaches have shown some efficiency in generating measurable immune responses, but they have rarely led to tumor regression. It is therefore possible that tumors emerge with the capacity to down-regulate immune counterparts, through the local production of immunosuppressive molecules, such as IDO. Although it is known that IDO exerts suppressive effects on T cell functions, the mechanisms of IDO regulation in tumor cells remain to be characterized. Here, we demonstrate that activated T cells can induce functional IDO expression in breast and kidney tumor cell lines, and that this is partly attributable to IFN-γ. Moreover, we found that IL-13, a Th2 cytokine, has a negative modulatory effect on IDO expression. Furthermore, we report IDO expression in the majority of breast and kidney carcinoma samples, with infiltration of activated Th1-polarized T cells in human tumors. These findings demonstrate complex control of immune activity within tumors. Future immune therapeutic interventions should thus include strategies to counteract these negative mechanisms.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Human Activated T Lymphocytes Modulate IDO Expression in Tumors through Th1/Th2 Balance

Godin-Ethier

Pelletier

Hanafi

et al. 2009

The Journal of Immunology

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“…Following vaccination an accumulation of IDO-expressing DCs and regulatory T cells was observed at the injection site. All patients had a rapid progressive disease and a short overall survival (35).…”

Section: Discussionmentioning

confidence: 99%

The properties of human CD40-activated B cells as antigen-presenting cells are not affected by PGE2

Shimabukuro‐Vornhagen

Draube

Liebig

et al. 2012

Oncology Reports

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Abstract. Tumor vaccination represents a promising immunotherapeutic strategy in cancer. However, the inherent ability of many tumors to evade immune responses by suppression of immune cell function represents a major barrier. Prostaglandin E 2 (PGE 2 ) has been shown to be a critical tumor-derived immunosuppressive factor. It affects a broad range of immune cells including T cells, macrophages and dendritic cells (DCs). CD40-activated B cells are being studied as a potential alternative to DCs as antigen-presenting cells for immunotherapy. So far, it is not known whether PGE 2 affects their antigen presenting capacity. We, therefore, investigated the influence of PGE 2 on the phenotype, migratory potential and antigen-presenting function of CD40-activated human B cells. Here, we demonstrate that the immunostimulatory properties of CD40-activated B cells are not affected by PGE 2 . These results support the use of CD40-activated B cells as cellular adjuvants, especially in settings where PGE 2 is present in the tumor microenvironment.

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“…adjuvants like TLR9 agonist CpG (Mellor et al, 2005;Wingender et al 2006). Moreover, it was reported by Wobser et al (2007) that the use of IL-1b, TNF, IL-6, and PGE 2 to stimulate in vitro DC generation resulted in upregulation of IDO expression in DC. On the other hand, inhibition of IDO activity by small molecules analogous to tryptophan, like 1-MT, elicited anti-tumor responses in experimental animal models and enhanced the effects of chemotherapy.…”

Section: Ido-dcmentioning

confidence: 99%

Breaking immunotolerance of tumors: A new perspective for dendritic cell therapy

Roliński¹,

Hus

2014

Journal of Immunotoxicology

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The use of dendritic cells (DC) in cancer immunotherapy is based on their potent abilities to present antigens, so they can act as 'natural adjuvants' to enhance immunogenicity of tumor antigens and stimulate specific cytotoxic T-cells. Large amounts of DC can be generated from bone marrow, neonatal cord blood, and peripheral blood CD34 þ hematopoietic stem cells, or from peripheral blood monocytes. The DC can then be pulsed with tumor antigens and reinfused. In vitro, antigen-pulsed DC can stimulate allogeneic T-cell proliferation and induction of autologous specific cytotoxic T-cells; in vivo, the cells inhibit the growth of tumors or protect hosts (i.e. mice) from development of inoculated tumors. The results of preliminary clinical trials have shown that DC vaccines are safe and elicit immune responses; however, the rates of clinical responses are low. It has become quite clear that one key reason for unsatisfactory clinical results is tumor-induced immunosuppression. Among the factors contributing to this type of immunosuppression are populations of regulatory cells including: T-regulatory (T reg ) cells, myeloid-derived suppressor cells (MDSC), tumor-associated macrophages (TAM), and DC expressing 2,3-dioxygenase indoleamine (IDO-DC). This review presents an overview of the current understanding about populations of regulatory cells and the most current research efforts directed to overcome immunosuppressive activity due to the tumor microenvironment.

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Dendritic cell based antitumor vaccination: impact of functional indoleamine 2,3-dioxygenase expression

Abstract: The presented observations suggest a potential clinical relevance of IDO expression in DC-based therapeutic vaccines via the attraction or induction of FoxP3(+) T-cells.

Cited by 65 publications

References 33 publications

Human Activated T Lymphocytes Modulate IDO Expression in Tumors through Th1/Th2 Balance

Human Activated T Lymphocytes Modulate IDO Expression in Tumors through Th1/Th2 Balance

The properties of human CD40-activated B cells as antigen-presenting cells are not affected by PGE2

Breaking immunotolerance of tumors: A new perspective for dendritic cell therapy

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