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 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.

scholarly journals Immature Dendritic Cells Phagocytose Apoptotic Cells via αvβ5 and CD36, and Cross-present Antigens to Cytotoxic T Lymphocytes

1998 ◽  
Vol 188 (7) ◽  
pp. 1359-1368 ◽  
Author(s):  
Matthew L. Albert ◽  
S.Frieda A. Pearce ◽  
Loise M. Francisco ◽  
Birthe Sauter ◽  
Pampa Roy ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Critical Role ◽  
Immature Stage ◽  
Apoptotic Cells ◽  
Cross Tolerance ◽  
Phagocytic Capacity ◽  
Immature Dendritic Cells ◽  
Antigenic Material

Dendritic cells, but not macrophages, efficiently phagocytose apoptotic cells and cross-present viral, tumor, and self-antigens to CD8+ T cells. This in vitro pathway corresponds to the in vivo phenomena of cross-priming and cross-tolerance. Here, we demonstrate that phagocytosis of apoptotic cells is restricted to the immature stage of dendritic cell (DC) development, and that this process is accompanied by the expression of a unique profile of receptors, in particular the αvβ5 integrin and CD36. Upon maturation, these receptors and, in turn, the phagocytic capacity of DCs, are downmodulated. Macrophages engulf apoptotic cells more efficiently than DCs, and although they express many receptors that mediate this uptake, they lack the αvβ5 integrin. Furthermore, in contrast to DCs, macrophages fail to cross-present antigenic material contained within the engulfed apoptotic cells. Thus, DCs use unique pathways for the phagocytosis, processing, and presentation of antigen derived from apoptotic cells on class I major histocompatibility complex. We suggest that the αvβ5 integrin plays a critical role in the trafficking of exogenous antigen by immature DCs in this cross-priming pathway.

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.

Stressed apoptotic tumor cells stimulate dendritic cells and induce specific cytotoxic T cells

Blood ◽  
2002 ◽  
Vol 100 (12) ◽  
pp. 4108-4115 ◽  
Author(s):  
Hanping Feng ◽  
Yi Zeng ◽  
Michael W. Graner ◽  
Emmanuel Katsanis
Keyword(s):  
Dendritic Cells ◽  
Tumor Cells ◽  
Cytotoxic T Cells ◽  
Surface Expression ◽  
Interleukin 12 ◽  
Apoptotic Cells ◽  
T Helper 1 ◽  
Immature Dendritic Cells ◽  
Shock Proteins

We have previously reported that stressed apoptotic tumor cells are more immunogenic in vivo than nonstressed ones. Using confocal microscopy we have confirmed our previous observation that heat-stressed apoptotic 12B1-D1 leukemia cells(BCR-ABL+) express HSP60 and HSP72 on their surface. To explore how the immune system distinguishes stressed from nonstressed apoptotic tumor cells, we analyzed the responses of dendritic cells to these 2 types of apoptotic cells. We found that nonstressed and heat-stressed apoptotic 12B1-D1 cells were taken up by dendritic cells in a comparable fashion. However, when stressed apoptotic 12B1-D1 cells were coincubated with immature dendritic cells for 24 hours, this resulted in greater up-regulation of costimulatory molecules (CD40, CD80, and CD86) on the surface of dendritic cells. Moreover, stressed apoptotic 12B1-D1 cells were more effective in stimulating dendritic cells to secrete interleukin-12 (IL-12) and in enhancing their immunostimulatory functions in mixed leukocyte reactions. Furthermore, we demonstrated that immunization of mice with stressed apoptotic 12B1-D1 cells induced the secretion of T helper-1 (TH1) profile of cytokines by spleen cells. Splenocytes from mice immunized with stressed apoptotic cells, but not nonstressed ones, were capable of lysing 12B1-D1 and the parental 12B1 line, but not a B-cell leukemia line, A20. Our data indicate that stressed apoptotic tumor cells are capable of providing the necessary danger signals, likely through increased surface expression of heat shock proteins (HSPs), resulting in activation/maturation of dendritic cells and, ultimately, the generation of potent antitumor T-cell responses.

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.

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