Tumor-Infiltrating Dendritic Cells are Defective in Their Antigen-Presenting Function and Inducible B7 Expression

Chaux, Pascal; Favre, Nathalie; Bonnotte, Bernard; Moutet, Monique; Martin, Monique; Martin, François

doi:10.1007/978-1-4757-9966-8_86

Cited by 34 publications

(19 citation statements)

References 6 publications

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“…We have previously demonstrated that experimental tumors (43), as well as human tumors (44), are infiltrated by DCs. However, these tumor-infiltrating DCs are blocked in an immature and nonfunctional stage (45).…”

Section: Discussionmentioning

confidence: 99%

Dendritic Cells Trigger Tumor Cell Death by a Nitric Oxide-Dependent Mechanism

Nicolas

Cathelin

Larmonier

et al. 2007

The Journal of Immunology

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Dendritic cells (DCs) are well known for their capacity to induce adaptive antitumor immune response through Ag presentation and tumor-specific T cell activation. Recent findings reveal that besides this role, DCs may display additional antitumor effects. In this study, we provide evidence that LPS- or IFN-γ-activated rat bone marrow-derived dendritic cells (BMDCs) display killing properties against tumor cells. These cytotoxic BMDCs exhibit a mature DC phenotype, produce high amounts of IL-12, IL-6, and TNF-α, and retain their phagocytic properties. BMDC-mediated tumor cell killing requires cell-cell contact and depends on NO production, but not on perforin/granzyme or on death receptors. Furthermore, dead tumor cells do not exhibit characteristics of apoptosis. Thus, intratumoral LPS injections induce an increase of inducible NO synthase expression in tumor-infiltrating DCs associated with a significant arrest of tumor growth. Altogether, these results suggest that LPS-activated BMDCs represent powerful tumoricidal cells which enforce their potential as anticancer cellular vaccines.

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Section: Discussionmentioning

confidence: 99%

Dendritic Cells Trigger Tumor Cell Death by a Nitric Oxide-Dependent Mechanism

Nicolas

Cathelin

Larmonier

et al. 2007

The Journal of Immunology

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“…However, such treatment did not affect tumor progression. To determine why this therapy failed, and given numerous reports that tumors can interfere with dendropoiesis (8,20,34) or with dendritic cells function (11,14), we focused our attention on the tumor microenvironment to determine whether TIDCs in cytokinetreated animals were functionally competent to cross-prime specific T effector cells. We found that CMS4 tumors in animals treated with Flt3 ligand + GM-CSF were highly infiltrated by dendritic cells (versus nontreated tumors), with optimal TIDCs observed after 5 days of cytokine administration.…”

Section: Discussionmentioning

confidence: 99%

“…2 (32). Immature dendritic cells express low levels of costimulatory molecules on their surface, whereas mature dendritic cells have up-regulated levels of these markers, and tumors have been reported to induce or restrict TIDCs towards an immature phenotype (8,11,33). As shown in Fig.…”

Section: Cd11bmentioning

confidence: 95%

“…Typically, tumor-infiltrating dendritic cells (TIDC) express low levels of MHC class II molecules and lack expression of costimulatory molecules (11,12). Dendritic cells isolated from tumor-bearing mice and humans show significantly reduced abilities to activate peptide-specific CD8 + T cells and to stimulate allogeneic T cells when compared with normal control dendritic cells (13,14).…”

Section: Introductionmentioning

confidence: 99%

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Combinational FLt3 Ligand and Granulocyte Macrophage Colony-Stimulating Factor Treatment Promotes Enhanced Tumor Infiltration by Dendritic Cells and Antitumor CD8+ T-Cell Cross-priming but Is Ineffective as a Therapy

Berhanu

Huang

Alber³

et al. 2006

Cancer Research

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“…39,40 Anti-VEGF antibody restores antigenpresenting cell function in tumor-bearing mice, and antigenpresenting cell dysfunction was observed in mice receiving continuous VEGF infusion. 13,25 These results demonstrated that VEGF contributes to inhibition of antigen-presenting cell function, but the role of the individual VEGF receptors in this effect in vivo was unclear.…”

Section: Vegf Inhibits the Ability Of Dcs To Stimulate Allogeneic T Cmentioning

confidence: 99%

Distinct roles of VEGFR-1 and VEGFR-2 in the aberrant hematopoiesis associated with elevated levels of VEGF

Huang¹,

Chen²,

Dikov

et al. 2007

Blood

197

171

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Vascular endothelial growth factor (VEGF), a major factor in tumor-host interactions, plays a critical role in the aberrant hematopoiesis observed in cancer-bearing hosts. To dissect the roles of VEGF receptor (VEGFR)-1 and VEGFR-2 in cancer-associated hematopoiesis in vivo, we selectively stimulated VEGFR-1 and VEGFR-2 by continuous infusion of receptor-specific ligands or selective blockade with VEGF receptor-specific antibodies in mice infused with recombinant VEGF at levels observed in tumor-bearing animals. We found that the effect of VEGF on the accumulation of Gr1+CD11b+ cells is mediated by VEGFR-2, but that the 2 receptors have opposite effects on lymphocyte development. Pathophysiologic levels of VEGF strongly inhibit T-cell development via VEGFR-2, whereas VEGFR-1 signaling decreases this inhibition. VEGFR-1, and not VEGFR-2, signaling is responsible for the observed increase of splenic B cells. Both receptors are capable of inhibiting dendritic cell function. These data suggest that most of observed aberrant hematopoiesis caused by excess tumor-derived VEGF is mediated by VEGFR-2, and VEGFR-1 alone has very limited independent effects but clearly both positively and negatively modulates the effects of VEGFR-2. Our findings suggest that selective blockade of VEGFR-2 rather than of both receptors may optimally overcome the adverse hematologic consequences of elevated VEGF levels found in malignancy.

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Tumor-Infiltrating Dendritic Cells are Defective in Their Antigen-Presenting Function and Inducible B7 Expression

Cited by 34 publications

References 6 publications

Dendritic Cells Trigger Tumor Cell Death by a Nitric Oxide-Dependent Mechanism

Dendritic Cells Trigger Tumor Cell Death by a Nitric Oxide-Dependent Mechanism

Combinational FLt3 Ligand and Granulocyte Macrophage Colony-Stimulating Factor Treatment Promotes Enhanced Tumor Infiltration by Dendritic Cells and Antitumor CD8+ T-Cell Cross-priming but Is Ineffective as a Therapy

Distinct roles of VEGFR-1 and VEGFR-2 in the aberrant hematopoiesis associated with elevated levels of VEGF

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