Dendritic cells are significantly reduced in non-Hodgkin's lymphoma and express less CCR7 and CD62L

Fiore, Francesca; Bergwelt‐Baildon, Michael S. von; Drebber, Uta; Beyer, Marc; Попов, А. В.; Manzke, Oliver; Wickenhauser, Claudia; Baldus, S.; Schultze, Joachim L.

doi:10.1080/10428190500360971

Cited by 30 publications

(21 citation statements)

References 42 publications

(40 reference statements)

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“…There are several studies drawing the issue about dendritic cells and T cells in B-cell lymphomas (22,33,34). However, we found for the first time that the peritumoral distribution of S100 + cells and CD45RO + T cells was correlated with a favorable prognosis in DLBCL.…”

Section: Discussionmentioning

confidence: 52%

Distribution Patterns of Dendritic Cells and T Cells in Diffuse Large B-Cell Lymphomas Correlate with Prognoses

Chang

Huang

Jones

et al. 2007

Clinical Cancer Research

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Purpose: Diffuse large B-cell lymphoma (DLBCL), the most common subtype of non-Hodgkin's lymphomas, accounts for 30% to 40% of all lymphoma cases. However, long-term survival by current chemotherapy was achieved in only 40% of patients, warranting the development of novel therapeutic strategies including T-cell immunotherapy. However, the level of baseline immune activation in DLBCL is unclear. Experimental Design: The density and distribution of dendritic cells and T cells in 48 cases of primary DLBCL was evaluated by immunohistochemistry. Results: Increased numbers of intratumoral CD1a + dendritic cells and increased S100 + cells and CD45RO + T cells around the edges of the tumors were seen in 10 of 48 (21%), 9 of 48 (19%), and 10 of 48 (21%) cases and these were correlated with a favorable prognosis (P = 0.015; P = 0.070, and P = 0.017, respectively), along with increased granzyme B + T cells in tumor beds (P = 0.013). Increased peritumoral T cells were correlated with tumor expression of HLA-DR (r = 0.446; P = 0.002). Extranodal lymphomas showed fewer tumor-associated CD45RO + Tcells (r = -0.407; P = 0.001) and less conspicuous dendritic cell infiltrates. Conclusions: In DLBCL, the presence of baseline antitumor immune response is associated with favorable clinical outcome, and thus adjuvant T-cell immunotherapy may further boost treatment responses.

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Section: Discussionmentioning

confidence: 52%

Distribution Patterns of Dendritic Cells and T Cells in Diffuse Large B-Cell Lymphomas Correlate with Prognoses

Chang

Huang

Jones

et al. 2007

Clinical Cancer Research

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“…The characterization of dendritic cells in NHL and the expression of adhesion molecules, costimulatory molecules, chemokine receptors and activation markers have been analysed in a few studies. Significantly decreased expression of CD62L and CCR7, receptors necessary for lymph node homing, was identified in dendritic cells in NHL 86 . Dendritic cells are also phenotypically altered and reduced in number in NHL, potentially contributing to the loss of tumour control in these patients.…”

Section: The Role Of Chemokines and Their Receptors In The Migrationmentioning

confidence: 99%

The challenge of the microenvironment in B-cell lymphomas

Coupland

2011

Histopathology

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B-cell non-Hodgkin lymphomas (B-NHL) represent the most common malignant lymphoid neoplasms, with the majority of these arising from germinal centre or post-germinal centre B cells, due to (at least) a disruption of the different phases of normal B-cell development. The most common B-cell lymphoma subtypes include follicular lymphoma, diffuse large B-cell lymphoma, marginal zone lymphoma and mantle cell lymphoma. As with other malignancies, it has been demonstrated that the development and progression of B-cell lymphomas involves complex interactions between the neoplastic B-cells and the surrounding microenvironment, including stromal cells, the intratumoral vasculature, the various types of macrophages, as well as T-cells, including regulatory T-cells (also termed T-regs). The complex communications between the cell populations involves interplay between chemokines, chemokine receptors and adhesion molecules, and the balance between these determines whether there is a tumour cell growth promotion or inhibition. The demonstration of the importance of the microenvironment in B-NHL has been shown recently using methodologies such as gene expression profiling, and has been validated in some B-NHL lymphoma subtypes using other techniques, such as immunohistochemistry. This is particularly in the case of follicular lymphomas, in which both T-regs and macrophages have been demonstrated to have prognostic value. As such, the microenvironment of B-cell lymphomas represents a challenge to the development of therapeutic agents, requiring re-direction and inclusion of these non-neoplastic supportive cells into future treatment strategies.

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“…12 DCs are not only reduced in numbers especially in proximity of the cancer, [13][14][15] but are also characterized by an altered maturation phenotype, 1,16 which-at least in part-can be induced by factors such as IL10 or VEGF in maturing DCs in vitro. 1,13,17 Some early indications of the molecular mechanisms by which these factors might lead to the generation of tolerogenic DCs have recently been reported.…”

Section: Introductionmentioning

confidence: 99%

CD25 and indoleamine 2,3-dioxygenase are up-regulated by prostaglandin E2 and expressed by tumor-associated dendritic cells in vivo: additional mechanisms of T-cell inhibition

Bergwelt‐Baildon

Попов

Šarić

et al. 2006

Blood

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219

194

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Immune tolerance is a central mechanism counteracting tumor-specific immunity and preventing effective anticancer immunotherapy. Induction of tolerance requires a specific environment in which tolerogenic dendritic cells (DCs) play an essential role deviating the immune response away from effective immunity. It was recently shown that maturation of DCs in the presence of PGE2 results in upregulation of indoleamine 2,3-dioxygenase (IDO) providing a potential mechanism for the development of DC-mediated Tcell tolerance. Here, we extend these findings, demonstrating a concomitant induction of IDO and secretion of soluble CD25 after DC maturation in the presence of PGE2. While maturation of DCs induced IDO expression on transcriptional level, only integration of PGE2 signaling led to up-regulation of functional IDO protein as well as significant expression of cell-surface and soluble CD25 protein. As a consequence, T-cell proliferation and cytokine production were significantly inhibited, which was mediated mainly by IDO-induced tryptophan depletion. Of importance, we demonstrate that different carcinoma entities associated with elevated levels of PGE2 coexpress CD25 and IDO in peritumoral dendritic cells, suggesting that PGE2 might influence IDO expression in human DCs in the tumor environment. We therefore suggest PGE2 to be a mediator of early events during induction of immune tolerance in cancer.

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Dendritic cells are significantly reduced in non-Hodgkin's lymphoma and express less CCR7 and CD62L

Cited by 30 publications

References 42 publications

Distribution Patterns of Dendritic Cells and T Cells in Diffuse Large B-Cell Lymphomas Correlate with Prognoses

Distribution Patterns of Dendritic Cells and T Cells in Diffuse Large B-Cell Lymphomas Correlate with Prognoses

The challenge of the microenvironment in B-cell lymphomas

CD25 and indoleamine 2,3-dioxygenase are up-regulated by prostaglandin E2 and expressed by tumor-associated dendritic cells in vivo: additional mechanisms of T-cell inhibition

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