scholarly journals In Breast Carcinoma Tissue, Immature Dendritic Cells Reside within the Tumor, Whereas Mature Dendritic Cells Are Located in Peritumoral Areas

1999 ◽  
Vol 190 (10) ◽  
pp. 1417-1426 ◽  
Author(s):  
Diana Bell ◽  
Pascale Chomarat ◽  
Denise Broyles ◽  
George Netto ◽  
Ghada Moumneh Harb ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Breast Carcinoma ◽  
Tumor Cells ◽  
Tumor Bed ◽  
Carcinoma Tissue ◽  
Inflammatory Protein ◽  
Immature Dendritic Cells ◽  
Cytokeratin Expression ◽  
Secondary Lymphoid Organs

We have analyzed the presence of immature and mature dendritic cells (DCs) within adenocarcinoma of the breast using immunohistochemistry. Immature DCs were defined by expression of CD1a-, Langerin-, and intracellular major histocompatibility complex class II–rich vesicles. Mature DCs were defined by expression of CD83 and DC-Lamp. Breast carcinoma cells were defined by morphology and/or cytokeratin expression. We demonstrate two levels of heterogeneity of DCs infiltrating breast carcinoma tissue: (a) immature CD1a+ DCs, mostly of the Langerhans cell type (Langerin+), were retained within the tumor bed in 32/32 samples and (b) mature DCs, CD83+DC-Lamp+, present in 20/32 samples, are confined to peritumoral areas. The high numbers of immature DCs found in the tumor may be best explained by high levels of macrophage inflammatory protein 3α expression by virtually all tumor cells. Confirming the immature/mature DC compartmentalization pattern, in vitro–generated immature DCs adhere to the tumor cells, whereas mature DCs adhere selectively to peritumoral areas. In some cases, T cells are clustering around the mature DCs in peritumoral areas, thus resembling the DC–T cell clusters of secondary lymphoid organs, which are characteristic of ongoing immune reactions.

Higher CD1a Levels Correlate with PD-L1 Expression and Predict Worse Overall Survival in Triple-Negative Breast Carcinoma

Breast Care ◽  
2021 ◽  
pp. 1-9
Author(s):  
Jian Zheng ◽  
Yuntao Wei ◽  
Xiaoxi Li ◽  
Zhan Shen ◽  
Yong Zhang ◽  
...  
Keyword(s):  
Overall Survival ◽  
Dendritic Cells ◽  
Lymph Node ◽  
Breast Carcinoma ◽  
Triple Negative ◽  
Carcinoma Tissue ◽  
Kaplan Meier ◽  
Immature Dendritic Cells ◽  
Triple Negative Breast Carcinoma ◽  
High Median

Objective: The aim of this study was to measure the expression of PD-L1, CD1a (a marker for immature dendritic cells), and CD83 (a marker for mature dendritic cells) and further examine the associations of PD-L1, CD83, and CD1a with overall survival (OS) in triple-negative breast carcinoma patients. Methods: PD-L1, CD1a, and CD83 expression in breast carcinoma tissues and CD83 expression in lymph node tissues were examined by immunohistochemistry and tissue microarray in 159 patients. Patients were classified into the low, medium, and high PD-L1, CD1a, and CD83 levels. Pearson χ2 test was used to analyze the correlations between PD-L1, CD1a, and CD83. The Kaplan-Meier method was used to calculate the OS. Multivariate analysis was used to identify determinants of 3- and 5-year OS. Results: 25.1, 25.8, and 49.1% of the patients had low, medium, and high PD-L1 levels, respectively. PD-L1 levels significantly correlated with CD1a (r = 0.30409, p < 0.001) and CD83 levels (r = 0.6146, p < 0.001) in breast carcinoma tissue, as well as CD83 levels (r = 0.17508, p = 0.027) in lymph node. The median OS was 83 months (range 12–106), and the 3- and 5-year OS rates were 94.97% (95% CI 91.57–98.37) and 86.79% (95% CI 81.53–92.06), respectively. Moreover, patients with high median CD1a levels had a significantly lower 5-year OS rate (75.6%) than those with low median CD1a levels (93.5%, p = 0.038). Conclusion: PD-L1, CD1a, and CD83 are variably expressed in triple-negative breast carcinoma tissues, and PD-L1 expression correlates with CD1a and CD83. Higher CD1a levels correlate with PD-L1 expression and predict worse OS in triple-negative breast carcinoma.

In vitro maturation and migration of immature dendritic cells after chemokine receptor 7 transfection

2009 ◽  
Vol 55 (7) ◽  
pp. 859-866 ◽  
Author(s):  
Hai-ming Xin ◽  
Yi-zhi Peng ◽  
Zhi-qiang Yuan ◽  
Hao Guo
Keyword(s):  
Dendritic Cells ◽  
Immune Tolerance ◽  
Chemokine Receptor ◽  
Recombinant Adenovirus ◽  
Gene Transfection ◽  
Interleukin 10 ◽  
Lymphoid Organs ◽  
Immature Dendritic Cells ◽  
Secondary Lymphoid Organs

Dendritic cells are specialized antigen-presenting cells that regulate immunity and tolerance. Chemokine receptor 7 (CCR7), which is expressed by mature dendritic cells, mediates the migration of the cells to secondary lymphoid organs and thus regulates immune responses. It has been demonstrated that immature dendritic cells can induce immune tolerance, but they do not express CCR7 and cannot migrate to secondary lymphoid organs. We transfected immature dendritic cells with a recombinant adenovirus carrying the CCR7 gene to obtain immature dendritic cells with the ability to migrate. The maturity of the cells was monitored by scanning electron microscopy and flow cytometry. In addition, we assessed the ability of cells to migrate and the function of the cells using in vitro chemotactic and mixed leukocyte reaction assays. The results showed that immature dendritic cells became semi-mature, exhibiting a mild upregulation of co-stimulatory molecular expression and a few dendritic processes. Immunofluorescence assay and Western blotting indicated that CCR7 protein expression increased significantly in immature dendritic cells following CCR7 gene transfection. The in vitro chemotactic assay showed a significantly enhanced ability to migrate in response to CCL19 following CCR7 gene transfection. Moreover, transfected cells showed an enhanced ability to stimulate allogeneic T cell proliferation in vitro, but their ability was significantly weaker than that of mature dendritic cells. Interleukin-10 inhibited the differentiation and maturation of immature dendritic cells. It is concluded that, following CCR7 gene transfection, immature dendritic cells exhibit an enhanced ability to migrate and some of the characteristics of mature cells. Thus, these cells are of potential clinical significance in studies of immune tolerance induction during skin grafting after severe burns.

Dendritic Cells Derived from K562/A02 Cell Line Treated by Recombinant Adenovirus Encoding Human p53

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4928-4928
Author(s):  
Lian-Sheng Zhang ◽  
Lijuan Li
Keyword(s):  
Dendritic Cells ◽  
Multidrug Resistance ◽  
Immune Responses ◽  
Tumor Cells ◽  
P53 Protein ◽  
P53 Gene ◽  
Multidrug Resistant ◽  
Leukemic Cells ◽  
Immature Dendritic Cells

Abstract Purpose Leukemia, a malignant tumor derived from hemotological system, belongs to a malignant clone disease of hemopoietic stem cell. Studies of immunology have indicated a close relationship between occurrence and development of leukemia and immunity of organism. Immunotherapy can completely clear up residual leukemic cells and cure the disease. The occurrence of multidrug resistance ( MDR ) is known for the main barrier of leukemia chemical therapy. And also, dendritic cells ( DCs ) are the most potent antigen-presenting cells for initiating cellular immune responses in vivo. DCs are attractive immunoregulatory cells for cancer immunotherapy, and their efficacy has been investigated in clinical trials. If we can induce multidrug resistant leukemic cell into a DC which is named with multidrug resistant leukemia-derived DC and promote its maturity with effective and harmless drugs, multidrug resistant leukemia-derived DC not only carries the special antigens of leukemia but also can present the special antigens to immune system to kill corresponding leukemic cells. At the same time, it can reverse indirectly leukemic multidrug resistance. Tumor suppressor gene p53 is pivotal in the regulation of apoptosis, and p53-based immunization is an attractive approach to cancer immunotherapy because of the mutant of p53 protein in malignant but not in normal cells. It has been shown that monocyte-derived human dendritic cells transduced with an adenoviral wild-type p53 (wt-p53) construct mediate the antitumor immune responses against p53-overexpressing tumor cells. We examined whether K562/A02 Cells -derived dendritic cells pulsed with the purified full-length wt-p53 protein were also capable of inducing the specific antitumor responses against K562/A02 cells in vitro. Methods P53 gene was transferred to monoclonal K562/A02 cells. P53 gene transcription was detected with RT-PCR. Proliferation test was conducted by using 3H-thymidine (3H-TdR) incorporation. Immature dendritic cells generated in the presence of interleukin-4 and granulocyte/macrophage colony-stimulating factor from K562/A02 cell line were transduced with an wt-p53. Uptake of p53 protein by dendritic cells was assessed by Western blotting. Induction of p53-specific CTL response was also evaluated by the cytotoxic assay against K562/A02 cells. Results Both Western blotting and and immunohistochemical analysis showed the accumulation of p53 protein in immature dendritic cells. T cells obtained from peripheral blood mononuclear cells of healthy volunteers were stimulated with wt-p53 and then applied to the cytotoxicity assay against the target cells-K562/A02. The CTL activity generated by adenoviral wt-p53-transduced dendritic cells was specific for K562/A02 cells. Conclusion Our results indicate that adenoviral wt-p53-transduced dendritic cells could induce the specific antitumor effect against the target tumor cells and that this in vitro model offers a new and more simple approach to the development of p53 and dendritic cellsbased immunogenetherapy. This offers a novel and promising immunogenetherapeutic srtategy to overcome multidrug resistant leukemia in the future.

Release of iC3b from apoptotic tumor cells induces tolerance by binding to immature dendritic cells in vitro and in vivo

2005 ◽  
Vol 55 (1) ◽  
pp. 31-38 ◽  
Author(s):  
Jan Schmidt ◽  
Christoph Klempp ◽  
Markus W. Büchler ◽  
Angela Märten
Keyword(s):  
Dendritic Cells ◽  
Tumor Cells ◽  
Immature Dendritic Cells

scholarly journals Adenovirus-Mediated CCR7 and BTLA Overexpression Enhances Immune Tolerance and Migration in Immature Dendritic Cells

2017 ◽  
Vol 2017 ◽  
pp. 1-8 ◽  
Author(s):  
Haiming Xin ◽  
Jinhong Zhu ◽  
Hongcheng Miao ◽  
Zhenyu Gong ◽  
Xiaochen Jiang ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Immune Tolerance ◽  
Transplant Recipients ◽  
T Helper ◽  
T Helper 2 ◽  
Immature Dendritic Cells ◽  
And Migration ◽  
Mixed Lymphocyte Reactions ◽  
Dc Maturation

Our previous report revealed that immature dendritic cells (imDCs) with adenovirus-mediated CCR7 overexpression acquired an enhanced migratory ability but also exhibited the lower immune tolerance observed in more mature cells. In the present study, we aimed to investigate whether BTLA overexpression was sufficient to preserve immune tolerance in imDCs with exogenous CCR7 overexpression. Scanning electron microscopy and surface antigens analysis revealed that BTLA overexpression suppressed DC maturation, an effect further potentiated in CCR7 and BTLA cooverexpressing cells. Correspondingly, in vitro chemotaxis assays and mixed lymphocyte reactions demonstrated increased migratory potential and immune tolerance in CCR7 and BTLA coexpressing cells. Furthermore, CCR7 and BTLA cooverexpressed imDCs suppressed IFN-γ and IL-17 expression and promoted IL-4 and TGF-beta expression of lymphocyte, indicating an increase of T helper 2 (Th2) regulatory T cell (Treg). Thus, these data indicate that CCR7 and BTLA cooverexpression imparts an intermediate immune phenotype in imDCs when compared to that in CCR7- or BTLA-expressing counterparts that show a more immunocompetent or immunotolerant phenotype, respectively. All these results indicated that adenovirus-mediated CCR7 and BTLA overexpression could enhance immune tolerance and migration of imDCs. Our study provides a basis for further studies on imDCs in immune tolerance, with the goal of developing effective cellular immunotherapies for transplant recipients.

Differential expression of Rel/NF-κB and octamer factors is a hallmark of the generation and maturation of dendritic cells

Blood ◽  
2000 ◽  
Vol 95 (1) ◽  
pp. 277-285 ◽  
Author(s):  
M. Neumann ◽  
H.-W. Fries ◽  
C. Scheicher ◽  
P. Keikavoussi ◽  
A. Kolb-Mäurer ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Differential Expression ◽  
Antigen Processing ◽  
Nuclear Translocation ◽  
Maturation Stage ◽  
Down Regulation ◽  
Immature Dendritic Cells ◽  
Monocytes And Macrophages ◽  
Induced Changes

Abstract A key feature of maturation of dendritic cells is the down-regulation of antigen-processing and up-regulation of immunostimulatory capacities. To study the differential expression of transcription factors in this process, we investigated the nuclear translocation and DNA binding of Rel/NF-κB and octamer factors during in vitro generation and maturation of dendritic cells compared with macrophage development. RelB was the only factor strongly up-regulated during the generation of both immature dendritic cells and macrophages. Cytokine-induced maturation of dendritic cells resulted in an increase in nuclear RelB, p50, p52, and especially c-Rel, whereas cytokine-treated macrophages responded poorly. This up-regulation of NF-κB factors did not correlate with lower levels of cytosolic NF-κB inhibitors, the IκBs. One IκB, Bcl-3, was strongly expressed only in mature dendritic cells. Furthermore, generation and maturation of dendritic cells led to a continuous down-regulation of the octamer factor Oct-2, whereas monocytes and macrophages displayed high Oct-2 levels. A similar pattern of maturation-induced changes in transcription factor levels was found in cultured murine epidermal Langerhans cells, suggesting a general physiological significance of these findings. Finally, this pattern of differential activation of Rel and octamer factors appears to be suitable in determining the maturation stage of dendritic cells generated by treatment with different cytokine combinations in vitro. (Blood. 2000;95:277-285)

scholarly journals A Potential Antitumor Effect of Dendritic Cells Fused with Cancer Stem Cells in Hepatocellular Carcinoma

2019 ◽  
Vol 2019 ◽  
pp. 1-10 ◽  
Author(s):  
Ye-Bin Pang ◽  
Jian He ◽  
Bi-Yu Cui ◽  
Sheng Xu ◽  
Xi-Lei Li ◽  
...  
Keyword(s):  
Stem Cells ◽  
Dendritic Cells ◽  
Stem Cell ◽  
Tumor Cells ◽  
Hepg2 Cells ◽  
Cytotoxicity Assay ◽  
Tumor Stem Cell ◽  
Fusion Cell

HCC stem cells were reported as posttreatment residual tumor cells that play a pivotal role in tumor relapse. Fusing dendritic cells (DCs) with tumor cells represents an ideal approach to effectively activate the antitumor immunity in vivo. DC/HCC stem cell vaccine provides a potential strategy to generate polyclonal immune response to multiple tumor stem cell antigens including those yet to be unidentified. To assess the potential capacity of DC/HCC stem cell vaccines against HCC, CD90+HepG2 cells were sorted from the HCC cell line HepG2. DC and CD90+HepG2 and DC and HepG2 fused cells were induced by polyethylene glycol (PEG). The influence of fusion cells on proliferation and immunological function transformation of lymphocytes was assessed by FCM and ELISA assay, respectively. The cytotoxicity assay of specific fusion cell-induced CTLs against HepG2 was conducted by CytoTox 96 Non-Radioactive Cytotoxicity Assay kit in vitro. At last, the prevention of HCC formation in vivo was described in a mouse model. The results of FCM analysis showed that the proportion of CD90+HepG2 cells in the spheral CD90+HepG2 enriched by suspension sphere culture was ranging from 98.7% to 99.5%, and 57.1% CD90+HepG2/DC fused cells were successfully constructed. The fusion cells expressed a higher level of costimulatory molecules CD80, CD83, CD86, and MHC-I and MHC-II molecules HLA-ABC and HLA-DR than did immature DCs (P<0.05). And the functional analysis of fusion cell-induced CTLs also illustrated that CD90+HepG2/DC fusion cells showed a greater capacity to activate proliferation of lymphocytes in vitro (P<0.05). The CD90+HepG2/DC-activated CTLs had a specific killing ability against CD90+HepG2 cells in vivo. These results suggested that CD90+HepG2/DC fusion cells could efficiently stimulate T lymphocytes to generate specific CTLs targeting CD90+HepG2 cells. It might be a promising strategy of immunotherapy for HCC.

Differential expression of Rel/NF-κB and octamer factors is a hallmark of the generation and maturation of dendritic cells

Blood ◽  
2000 ◽  
Vol 95 (1) ◽  
pp. 277-285 ◽  
Author(s):  
M. Neumann ◽  
H.-W. Fries ◽  
C. Scheicher ◽  
P. Keikavoussi ◽  
A. Kolb-Mäurer ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Differential Expression ◽  
Antigen Processing ◽  
Nuclear Translocation ◽  
Maturation Stage ◽  
Down Regulation ◽  
Immature Dendritic Cells ◽  
Monocytes And Macrophages ◽  
Induced Changes

A key feature of maturation of dendritic cells is the down-regulation of antigen-processing and up-regulation of immunostimulatory capacities. To study the differential expression of transcription factors in this process, we investigated the nuclear translocation and DNA binding of Rel/NF-κB and octamer factors during in vitro generation and maturation of dendritic cells compared with macrophage development. RelB was the only factor strongly up-regulated during the generation of both immature dendritic cells and macrophages. Cytokine-induced maturation of dendritic cells resulted in an increase in nuclear RelB, p50, p52, and especially c-Rel, whereas cytokine-treated macrophages responded poorly. This up-regulation of NF-κB factors did not correlate with lower levels of cytosolic NF-κB inhibitors, the IκBs. One IκB, Bcl-3, was strongly expressed only in mature dendritic cells. Furthermore, generation and maturation of dendritic cells led to a continuous down-regulation of the octamer factor Oct-2, whereas monocytes and macrophages displayed high Oct-2 levels. A similar pattern of maturation-induced changes in transcription factor levels was found in cultured murine epidermal Langerhans cells, suggesting a general physiological significance of these findings. Finally, this pattern of differential activation of Rel and octamer factors appears to be suitable in determining the maturation stage of dendritic cells generated by treatment with different cytokine combinations in vitro. (Blood. 2000;95:277-285)

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