scholarly journals Modern strategies and capabilities for activation of the immune response against tumor cells

Tumor Biology ◽  
2017 ◽  
Vol 39 (5) ◽  
pp. 101042831769838 ◽  
Author(s):  
Sergey Vital’evich Sennikov ◽  
Julia Nikolaevna Khantakova ◽  
Ekaterina Vladimirovna Kulikova ◽  
Irina Alexandrovna Obleukhova ◽  
Julia Alexandrovna Shevchenko
Keyword(s):  
Immune Response ◽  
Dendritic Cells ◽  
Immune Responses ◽  
Malignant Tumors ◽  
Active Form ◽  
Antitumor Immune Response ◽  
Antigen Presenting ◽  
Additional Stimulation ◽  
Naive T Lymphocytes

Dendritic cells are professional antigen-presenting cells and the most potent stimulators of various immune responses, such as antitumor responses. Modern studies have not shown an effective antitumor immune response development in patients with malignant tumors. The major cause is the decrease in functional activity of dendritic cells in cancer patients through irregularities in the maturation process to a functionally active form and in the antigen presentation process to naive T lymphocytes. This review describes the main stages of cellular antitumor immune response induction in vitro, aimed at resolving the problems that are blocking the full functioning of dendritic cells, and additional stimulation of antitumor immune response.

scholarly journals Downregulation of L-arginine metabolism in dendritic cells induces tolerance to exogenous antigen

2017 ◽  
Vol 30 (1) ◽  
pp. 44-57 ◽  
Author(s):  
Patricia U Simioni ◽  
Luis GR Fernandes ◽  
Wirla MSC Tamashiro
Keyword(s):  
Immune Response ◽  
Dendritic Cells ◽  
Immune Responses ◽  
Adoptive Transfer ◽  
Arginine Metabolism ◽  
Exogenous Antigen ◽  
Microbial Products ◽  
Oxide Synthase ◽  
Important Therapeutic Target

Dendritic cells (DC) are potential tools for therapeutic applications and several strategies to generate tolerogenic DCs are under investigation. When activated by cytokines and microbial products, DCs express mediators that modulate immune responses. In this regard, the metabolites generated by the activities of inducible nitric oxide synthase (iNOS) and arginase in DCs seem to play important roles. Here, we evaluated the effects of adoptive transfer of DCs generated in vitro from bone marrow precursors (BMDC) modulated with L-NAME (Nω-nitro-L-arginine methyl ester) and NOHA (NG-Hydroxy-L-arginine), inhibitors of iNOS and arginase, respectively, upon the immune response of the wild type (BALB/c) and OVA-TCR transgenic (DO11.10) mice. The modulation with L-NAME increased CD86 expression in BMDC, whereas treatment with NOHA increased both CD80 and CD86 expression. Adoptive transfer of either L-NAME- or NOHA-modulated BMDCs to BALB/c mice reduced the plasma levels of ovalbumin-specific antibody as well as proliferation and cytokine secretion in cultures of spleen cells in comparison adoptive transfer of non-modulated DCs. Conversely, transfer of both modulated and non-modulated BMDCs had no effect on immune response of DO11.10 mice. Together, these results show that the treatment with iNOS and Arg inhibitors leads to increased expression of co-stimulatory molecules in DCs, and provides evidences that L-arginine metabolism may be an important therapeutic target for modulating immune responses in inflammatory disorders.

scholarly journals Similar antigen cross-presentation capacity and phagocytic functions in all freshly isolated human lymphoid organ–resident dendritic cells

2013 ◽  
Vol 210 (5) ◽  
pp. 1035-1047 ◽  
Author(s):  
Elodie Segura ◽  
Mélanie Durand ◽  
Sebastian Amigorena
Keyword(s):  
Dendritic Cells ◽  
Immune Responses ◽  
Lymphoid Organ ◽  
Lymphoid Organs ◽  
Endocytic Pathway ◽  
Soluble Antigen ◽  
Cross Presentation ◽  
Antigen Presenting ◽  
Secondary Lymphoid Organs

Dendritic cells (DCs) represent a heterogeneous population of antigen-presenting cells that initiate and orient immune responses in secondary lymphoid organs. In mice, lymphoid organ–resident CD8+ DCs are specialized at cross-presentation and have developed specific adaptations of their endocytic pathway (high pH, low degradation, and high export to the cytosol). In humans, blood BDCA3+ DCs were recently shown to be the homologues of mouse CD8+ DCs. They were also proposed to cross-present antigens more efficiently than other blood DC subsets after in vitro activation, suggesting that in humans cross-presentation is restricted to certain DC subsets. The DCs that cross-present antigen physiologically, however, are the ones present in lymphoid organs. Here, we show that freshly isolated tonsil-resident BDCA1+ DCs, BDCA3+ DCs, and pDCs all cross-present soluble antigen efficiently, as compared to macrophages, in the absence of activation. In addition, BDCA1+ and BDCA3+ DCs display similar phagosomal pH and similar production of reactive oxygen species in their phagosomes. All three DC subsets, in contrast to macrophages, also efficiently export internalized proteins to the cytosol. We conclude that all freshly isolated lymphoid organ–resident human DCs, but not macrophages, display high intrinsic cross-presentation capacity.

Antibody Response after Vaccination with Antigen-Pulsed Dendritic Cells

2004 ◽  
Vol 19 (3) ◽  
pp. 213-220
Author(s):  
F. Battaini ◽  
D. Besusso ◽  
L. Sfondrini ◽  
A. Rossini ◽  
D. Morelli ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Immune System ◽  
Immune Responses ◽  
Antibody Response ◽  
Cancer Patients ◽  
Antibody Production ◽  
Tumor Antigens ◽  
Antigen Uptake ◽  
Antigen Presenting

Dendritic cells (DCs) are the most potent antigen-presenting cells of the immune system capable of initiating immune responses to antigens. It is also well documented that cancer patients often experience anergy against tumor antigens. In this study we selected the best protocol for inducing the production of antibodies against the HER2 oncoprotein using DCs to overcome anergy. Murine DCs were pulsed in vitro, using different protocols, with recombinant HER2 fused to a human Fc (in order to improve DC antigen uptake) and were used to vaccinate mice. The obtained results indicate that antigen-pulsed DCs can induce an antibody response and that adding CpG after antigen pulsing greatly increases anti-HER2 antibody production.

Isolation of Human Blood Dendritic Cells Using the CMRF-44 Monoclonal Antibody: Implications for Studies on Antigen-Presenting Cell Function and Immunotherapy

Blood ◽  
1997 ◽  
Vol 89 (10) ◽  
pp. 3708-3716 ◽  
Author(s):  
D.B. Fearnley ◽  
A.D. McLellan ◽  
S.I. Mannering ◽  
B.D. Hock ◽  
D.N.J. Hart
Keyword(s):  
Monoclonal Antibody ◽  
Dendritic Cells ◽  
Immune Responses ◽  
Cell Function ◽  
Cell Clone ◽  
Antigen Uptake ◽  
T Cell Clone ◽  
Antigen Presenting ◽  
Dc Maturation

Abstract Dendritic cells (DC) are potent antigen-presenting cells (APC) with the capacity to stimulate a primary T lymphocyte immune response and are therefore of interest for potential immunotherapeutic applications. Freshly isolated DC or DC precursors may be preferable for studies of antigen uptake and the potential control of APC costimulator activity. In this report, we report that the monoclonal antibody CMRF-44 can be used to detect early DC differentiation. The majority of DC circulating in blood do not express any known DC lineage specific markers, but can be identified by CMRF-44 labeling after a brief period of in vitro culture. The sequential acquisition of DC activation antigens allows the identification of two stages of DC maturation/activation. Cytokines, especially granulocyte-macrophage colony-stimulating factor (GM-CSF ) and tumor necrosis factor (TNF )α, enhance both phases of this process, whereas CD40-ligand trimer preferentially enhances the final DC maturation to a fully mature, activated phenotype. DC positively selected using CMRF-44 possess potent allostimulatory activity and are efficient at the uptake, processing, and presentation of soluble antigens for both primary and secondary immune responses. CMRF-44+ DC are also more potent than other APC types at restimulation of a chronic myeloid leukemia peptide specific T-cell clone. The use of a purified population of freshly isolated DC may be advantageous in attempts to initiate, maintain, and direct immune responses for immunotherapeutic applications.

scholarly journals Leptin’s and antigen-presenting cells’ functions in periodontitis – an overview / Leptin e as funções das células que apresentam antigénios na periodontite - uma visão geral

2021 ◽  
Vol 4 (2) ◽  
pp. 8011-8019
Author(s):  
Giovanna Ganem Favero ◽  
Isabela Lopes Martin ◽  
Fernanda Pereira da Silva Albino ◽  
Carlos Eduardo Fontana ◽  
Sérgio Luiz Pinheiro ◽  
...  
Keyword(s):  
Immune Response ◽  
Dendritic Cells ◽  
Immune Responses ◽  
Inflammatory Responses ◽  
Antigen Presenting Cells ◽  
Adaptive Immune Responses ◽  
Adaptive Immune ◽  
Inflammatory Immune Response ◽  
Antigen Presenting ◽  
The Relationship

Leptin is a hormone synthesized predominantly by white adipose tissue. Its production levels are directly proportional to the total mass of this tissue in an individual’s body. Apart from its classic role in the regulation of hunger and satiety, it also plays an important part in scenarios involving innate and adaptive immune responses. It has been discovered that leptin levels are altered in a variety of inflammatory responses, such as periodontitis, a condition which derives from a persistent inflammatory immune response from a host facing bacterial infection. The initial trigger for this reaction is the recognition of the pathogens by antigen presenting cells, such as macrophages and dendritic cells, whose actions can be influenced by leptin. This review aims to present the relationship between leptin, dendritic cells and macrophages in the context of periodontal disease. Thus, we have assembled the most important findings related to leptin’s role in the modulation of the immune response carried out by these cells in periodontitis.

scholarly journals Isolation of Human Blood Dendritic Cells Using the CMRF-44 Monoclonal Antibody: Implications for Studies on Antigen-Presenting Cell Function and Immunotherapy

Blood ◽  
1997 ◽  
Vol 89 (10) ◽  
pp. 3708-3716 ◽  
Author(s):  
D.B. Fearnley ◽  
A.D. McLellan ◽  
S.I. Mannering ◽  
B.D. Hock ◽  
D.N.J. Hart
Keyword(s):  
Monoclonal Antibody ◽  
Dendritic Cells ◽  
Immune Responses ◽  
Cell Function ◽  
Cell Clone ◽  
Antigen Uptake ◽  
T Cell Clone ◽  
Antigen Presenting ◽  
Dc Maturation

Dendritic cells (DC) are potent antigen-presenting cells (APC) with the capacity to stimulate a primary T lymphocyte immune response and are therefore of interest for potential immunotherapeutic applications. Freshly isolated DC or DC precursors may be preferable for studies of antigen uptake and the potential control of APC costimulator activity. In this report, we report that the monoclonal antibody CMRF-44 can be used to detect early DC differentiation. The majority of DC circulating in blood do not express any known DC lineage specific markers, but can be identified by CMRF-44 labeling after a brief period of in vitro culture. The sequential acquisition of DC activation antigens allows the identification of two stages of DC maturation/activation. Cytokines, especially granulocyte-macrophage colony-stimulating factor (GM-CSF ) and tumor necrosis factor (TNF )α, enhance both phases of this process, whereas CD40-ligand trimer preferentially enhances the final DC maturation to a fully mature, activated phenotype. DC positively selected using CMRF-44 possess potent allostimulatory activity and are efficient at the uptake, processing, and presentation of soluble antigens for both primary and secondary immune responses. CMRF-44+ DC are also more potent than other APC types at restimulation of a chronic myeloid leukemia peptide specific T-cell clone. The use of a purified population of freshly isolated DC may be advantageous in attempts to initiate, maintain, and direct immune responses for immunotherapeutic applications.

scholarly journals Fate of Mycobacterium tuberculosis within Murine Dendritic Cells

2001 ◽  
Vol 69 (2) ◽  
pp. 800-809 ◽  
Author(s):  
Kendra A. Bodnar ◽  
Natalya V. Serbina ◽  
JoAnne L. Flynn
Keyword(s):  
Nitric Oxide ◽  
Bone Marrow ◽  
Immune Response ◽  
Dendritic Cells ◽  
Mycobacterium Tuberculosis ◽  
Immune Responses ◽  
Intracellular Bacteria ◽  
Murine Bone Marrow ◽  
Oxide Synthase

ABSTRACT The interaction of microbes with dendritic cells (DCs) is likely to have an enormous impact on the initiation of the immune response against a pathogen. In this study, we compared the interaction ofMycobacterium tuberculosis with murine bone marrow-derived DCs and macrophages (Mφ) in vitro. M. tuberculosis grew equally well within nonactivated DCs and Mφ. Activation of DCs and Mφ with gamma interferon and lipopolysaccharide inhibited the growth of the intracellular bacteria in a nitric oxide synthase-dependent fashion. However, while this activation enabled Mφ to kill the intracellular bacteria, the M. tuberculosis bacilli within activated DCs were not killed. Thus, DCs could restrict the growth of the intracellular mycobacteria but were less efficient than Mφ at eliminating the infection. These results may have implications for priming immune responses to M. tuberculosis. In addition, they suggest that DCs may serve as a reservoir for M. tuberculosis in tissues, including the lymph nodes and lungs.

scholarly journals Strategies for Enhancing Vaccine-Induced CTL Antitumor Immune Responses

2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Xin Yong ◽  
Yü-Feng Xiao ◽  
Gang Luo ◽  
Bin He ◽  
Mu-Han Lü ◽  
...  
Keyword(s):  
Immune Response ◽  
Immune Responses ◽  
Tumor Cells ◽  
Tumor Antigens ◽  
Critical Role ◽  
Antitumor Immune Response ◽  
Tumor Vaccines ◽  
Cytotoxic Effects

Vaccine-induced cytotoxic T lymphocytes (CTLs) play a critical role in adaptive immunity against cancers. An important goal of current vaccine research is to induce durable and long-lasting functional CTLs that can mediate cytotoxic effects on tumor cells. To attain this goal, there are four distinct steps that must be achieved. To initiate a vaccine-induced CTL antitumor immune response, dendritic cells (DCs) must capture antigens derived from exogenous tumor vaccines in vivo or autologous DCs directly loaded in vitro with tumor antigens must be injected. Next, tumor-antigen-loaded DCs must activate CTLs in lymphoid organs. Subsequently, activated CTLs must enter the tumor microenvironment to perform their functions, at which point a variety of negative regulatory signals suppress the immune response. Finally, CTL-mediated cytotoxic effects must overcome the tolerance induced by tumor cells. Each step is a complex process that may be impeded in many ways. However, if these steps happen under appropriate regulation, the vaccine-induced CTL antitumor immune response will be more successful. For this reason, we should gain a better understanding of the basic mechanisms that govern the immune response. This paper, based on the steps necessary to induce an immune response, discusses current strategies for enhancing vaccine-induced CTL antitumor immune responses.

In vitro antitumor immune response induced by dendritic cells transduced with human livin α recombinant adenovirus

2015 ◽  
Vol 297 (1) ◽  
pp. 46-52 ◽  
Author(s):  
Junping Xie ◽  
Xiaolin Guo ◽  
Fangfang Liu ◽  
Junming Luo ◽  
Fengying Duan ◽  
...  
Keyword(s):  
Immune Response ◽  
Dendritic Cells ◽  
Recombinant Adenovirus ◽  
Antitumor Immune Response

scholarly journals Survival of Chlamydia muridarum within Dendritic Cells

2007 ◽  
Vol 75 (8) ◽  
pp. 3707-3714 ◽  
Author(s):  
Jose Rey-Ladino ◽  
Xiaozhou Jiang ◽  
Brent R. Gabel ◽  
Caixia Shen ◽  
Robert C. Brunham
Keyword(s):  
Dendritic Cells ◽  
Immune Responses ◽  
Lung Infection ◽  
T Cell Memory ◽  
Mouse Lung ◽  
Term Survival ◽  
Chlamydia Muridarum ◽  
Antigen Presenting

ABSTRACT Immune responses to Chlamydia trachomatis underlay both immunity and immunopathology. Immunopathology in turn has been attributed to chronic persistent infection with persistence being defined as the presence of organisms in the absence of replication. We hypothesized that dendritic cells (DCs) play a central role in Chlamydia immunity and immunopathology by favoring the long-term survival of C. muridarum. This hypothesis was examined based on (i) direct staining of Chlamydia in infected DCs to evaluate the development of inclusions, (ii) titration of infected DCs on HeLa cells to determine cultivability, and (iii) transfer of Chlamydia-infected DCs to naive mice to evaluate infectivity. The results show that Chlamydia survived within DCs and developed both typical and atypical inclusions that persisted in a subpopulation of DCs for more than 9 days after infection. Since the cultivability of Chlamydia from DCs onto HeLa was lower than that estimated by the number of inclusions in DCs, this suggests that the organisms may be in state of persistence. Intranasal transfer of long-term infected DCs or DCs purified from the lungs of infected mice caused mouse lung infection, suggesting that in addition to persistent forms, infective Chlamydia organisms also developed within chronically infected DCs. Interestingly, after in vitro infection with Chlamydia, most DCs died. However, Chlamydia appeared to survive in a subpopulation of DCs that resisted infection-induced cell death. Surviving DCs efficiently presented Chlamydia antigens to Chlamydia-specific CD4+ T cells, suggesting that the bacteria are able to both direct their own survival and still allow DC antigen-presenting function. Together, these results raise the possibility that Chlamydia-infected DCs may be central to the maintenance of T-cell memory that underlies both immunity and immunopathology.

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