scholarly journals Advances in Immunotherapy for Melanoma: A Comprehensive Review

2017 ◽  
Vol 2017 ◽  
pp. 1-14 ◽  
Author(s):  
Carmen Rodríguez-Cerdeira ◽  
Miguel Carnero Gregorio ◽  
Adriana López-Barcenas ◽  
Elena Sánchez-Blanco ◽  
Beatriz Sánchez-Blanco ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Immune Responses ◽  
Tumor Cells ◽  
Mortality Rates ◽  
Cellular Adhesion ◽  
Active Immunotherapy ◽  
Comprehensive Review ◽  
Dendritic Cell Vaccines ◽  
Experimental Approaches ◽  
Specific Active Immunotherapy

Melanomas are tumors originating from melanocytes and tend to show early metastasis secondary to the loss of cellular adhesion in the primary tumor, resulting in high mortality rates. Cancer-specific active immunotherapy is an experimental form of treatment that stimulates the immune system to recognize antigens on the surface of cancer cells. Current experimental approaches in immunotherapy include vaccines, biochemotherapy, and the transfer of adoptive T cells and dendritic cells. Several types of vaccines, including peptide, viral, and dendritic cell vaccines, are currently under investigation for the treatment of melanoma. These treatments have the same goal as drugs that are already used to stimulate the proliferation of T lymphocytes in order to destroy tumor cells; however, immunotherapies aim to selectively attack the tumor cells of each patient. In this comprehensive review, we describe recent advancements in the development of immunotherapies for melanoma, with a specific focus on the identification of neoantigens for the prediction of their elicited immune responses. This review is expected to provide important insights into the future of immunotherapy for melanoma.

Efficient migration of dendritic cells toward lymph node chemokines and induction of TH1 responses require maturation stimulus and apoptotic cell interaction

Blood ◽  
2005 ◽  
Vol 106 (5) ◽  
pp. 1734-1741 ◽  
Author(s):  
Nicolas Bertho ◽  
Henri Adamski ◽  
Louis Toujas ◽  
Martine Debove ◽  
Jean Davoust ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Lymph Node ◽  
Immune Responses ◽  
Tumor Cells ◽  
Apoptotic Cell ◽  
Apoptotic Cells ◽  
Naive T Cells ◽  
Naïve T Cells ◽  
Tnf Α

Abstract Dendritic cells (DCs) have the unique ability to initiate primary immune responses, and they can be conditioned for vaccinal purposes to present antigens after the engulfment of apoptotic cells. To recruit the rare antigen-specific naive T cells, DCs require a maturation step and subsequent transport toward lymph node (LN). To date, prostaglandin E2 (PGE2) is the best-characterized compound inducing this LN-directed migration in vitro, but PGE2 may skew the immune responses in a TH2 direction. We demonstrate here that on incubation with apoptotic tumor cells and tumor necrosis factor-α (TNF-α) or lipopolysaccharide (LPS), human monocyte-derived DCs become fully mature and acquire high migratory capacities toward LN-directing chemokines. The migration of TNF-α-treated DCs occurs only after cotreatment with apoptotic cells but not with necrotic cells. DC migration requires CD36 expression and incubation with apoptotic cells in the presence of heat-labile serum components. Moreover, on treatment with apoptotic cells and LPS, the migrating DCs are able to recruit naive T cells to generate TH1 immune responses. Our results show that the cotreatment of DCs with apoptotic tumor cells and inflammatory signals is promising for the design of an antitumoral DC-based vaccine. (Blood. 2005;106:1734-1741)

Manipulating dendritic cell biology for the active immunotherapy of cancer

Blood ◽  
2004 ◽  
Vol 104 (8) ◽  
pp. 2235-2246 ◽  
Author(s):  
David W. O'Neill ◽  
Sylvia Adams ◽  
Nina Bhardwaj
Keyword(s):  
Dendritic Cells ◽  
Immune Responses ◽  
Cell Biology ◽  
Active Immunotherapy ◽  
Transplantation Tolerance ◽  
Chronic Infections ◽  
Immunotherapy Of Cancer ◽  
Antigen Presenting ◽  
And Control ◽  
New Strategies

Abstract Dendritic cells (DCs) are specialized antigen-presenting cells (APCs) that have an unequaled capacity to initiate primary immune responses, including tolerogenic responses. Because of the importance of DCs in the induction and control of immunity, an understanding of their biology is central to the development of potent immunotherapies for cancer, chronic infections, autoimmune disease, and induction of transplantation tolerance. This review discusses recent advances in DC research and the application of this knowledge toward new strategies for the clinical manipulation of DCs for cancer immunotherapy.

Dendritic Cells Can Be Primed to Concurrently Activate Both Unconventional Gamma/delta and Conventional alpha/beta T Cells.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3893-3893
Author(s):  
Francesca Fiore ◽  
Barbara Castella ◽  
Barbara Nuschak ◽  
Raffaello Bertieri ◽  
Sara Mariani ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Immune Responses ◽  
Tumor Cells ◽  
Peripheral Blood ◽  
Adoptive Cell Therapy ◽  
Effector Memory ◽  
Gamma Delta T Cells ◽  
Gamma Delta ◽  
Alpha Beta

Abstract Vgamma9/Vdelta2 (gamma/delta) T cells represent the major subset of unconventional T cells circulating in the peripheral blood. Gamma/delta T cells play a major role in immune defenses against microbes, stressed cells and tumor cells. This property is based on their capability to naturally recognize phosphoantigens (pAgs), which are produced via the mevalonate (Mev) or the DOXP pathway in mammalian and nonmammalian cells, and induced self-ligands, which are de novo expressed or upregulated on the surface of stressed or tumor cells. Interestingly, gamma/delta T cells can also be activated by aminobisphosphonates (ABP)-treated monocytes. We have previously shown that ABP specifically target the Mev pathway of monocytes and induce the accumulation of phosphorylated Mev metabolites naturally recognized by gamma/delta T cells. The aim of this work was to determine whether ABP-treated dendritic cells (DC) can also activate gamma/delta T cells and whether this activation, if any, is detrimental or beneficial to the generation of antigen (Ag)-specific MHC-restricted immune responses mediated by conventional alpha/beta T cells. To this end, we have generated highly purified immature (iDC) and mature DC (mDC) from peripheral blood monocytes of healthy donors and incubated with zoledronic acid (Zol) for 24 hours. Zol is the most potent ABP currently available for clinical use. Zol treatment did not affect the phenotype and immunostimulatory properties of iDC and mDC. Zol-treated iDC and mDC induced a rapid and vigorous expansion of central memory and effector memory gamma/delta T cells. Zol-treated iDC were more potent inducers of gamma/delta T-cell activation than mDC and monocytes. Activated gamma/delta T cells displayed antitumor activity and expressed on the cell surface the appropriate antigen repertoire to target secondary lymphoid organs and exert costimulatory activity on conventional alpha/beta T cells. Indeed, an in vitro model showed that antigen-specific MHC-restricted immune responses againt the influenza matrix peptide were significantly improved by the concurrent activation of gamma/delta T cells. This is the first report showing that: 1) DC can simultaneously be primed to activate both gamma/delta and alpha/beta T cells; 2) the former act as cellular adjuvants for the development of adaptive immune responses. In conclusion, large numbers of gamma/delta T cells with effector and costimulatory activities can rapidly be generated by Zol-treated iDC/mDC. This strategy is worth of further investigation to improve adoptive cell therapy and vaccine interventions against tumors and infections.

scholarly journals Antigen-Specific Polyclonal Cytotoxic T Lymphocytes Induced by Fusions of Dendritic Cells and Tumor Cells

2010 ◽  
Vol 2010 ◽  
pp. 1-12 ◽  
Author(s):  
Shigeo Koido ◽  
Sadamu Homma ◽  
Eiichi Hara ◽  
Yoshihisa Namiki ◽  
Toshifumi Ohkusa ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
T Lymphocytes ◽  
Immune Responses ◽  
Tumor Cells ◽  
Cytotoxic T Lymphocytes ◽  
Alternative Approach ◽  
Antigen Presenting ◽  
Ctl Induction ◽  
Secondary Lymphoid Organs ◽  
Powerful Strategy

The aim of cancer vaccines is induction of tumor-specific cytotoxic T lymphocytes (CTLs) that can reduce the tumor mass. Dendritic cells (DCs) are potent antigen-presenting cells and play a central role in the initiation and regulation of primary immune responses. Thus, DCs-based vaccination represents a potentially powerful strategy for induction of antigen-specific CTLs. Fusions of DCs and whole tumor cells represent an alternative approach to deliver, process, and subsequently present a broad spectrum of antigens, including those known and unidentified, in the context of costimulatory molecules. Once DCs/tumor fusions have been infused back into patient, they migrate to secondary lymphoid organs, where the generation of antigen-specific polyclonal CTL responses occurs. We will discuss perspectives for future development of DCs/tumor fusions for CTL induction.

scholarly journals Recent Advances in Good Manufacturing Practice-Grade Generation of Dendritic Cells

2020 ◽  
Vol 47 (6) ◽  
pp. 454-463
Author(s):  
Sarah Cunningham ◽  
Holger Hackstein
Keyword(s):  
Dendritic Cells ◽  
Immune Responses ◽  
Adaptive Immune System ◽  
Good Manufacturing Practice ◽  
Clinical Applications ◽  
Small Scale ◽  
Adaptive Immune ◽  
Recent Advances ◽  
Experimental Approaches ◽  
Key Features

Dendritic cells (DCs) are pivotal regulators of immune responses, specialized in antigen presentation and bridging the gap between the innate and adaptive immune system. Due to these key features, DCs have become a pillar of the continuously growing field of cellular therapies. Here we review recent advances in good manufacturing practice strategies and their individual specificities in relation to DC production for clinical applications. These take into account both small-scale experimental approaches as well as automated systems for patient care.

scholarly journals Dendritic Cells Capture Killed Tumor Cells and Present Their Antigens to Elicit Tumor-Specific Immune Responses

2000 ◽  
Vol 165 (7) ◽  
pp. 3797-3803 ◽  
Author(s):  
Mahyar Nouri-Shirazi ◽  
Jacques Banchereau ◽  
Diana Bell ◽  
Susan Burkeholder ◽  
Elizabeth T. Kraus ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Immune Responses ◽  
Tumor Cells

Autologous dendritic cells loaded with apoptotic tumor cells induce T cell-mediated immune responses against breast cancer in vitro

2009 ◽  
Vol 257 (1-2) ◽  
pp. 23-31 ◽  
Author(s):  
Nowruz Delirezh ◽  
Seyed Mohammad Moazzeni ◽  
Fazel Shokri ◽  
Mohammad Ali Shokrgozar ◽  
Morteza Atri ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Dendritic Cells ◽  
T Cell ◽  
Immune Responses ◽  
Tumor Cells

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.

Dendritic cells in atherosclerosis: Functions in immune regulation and beyond

2011 ◽  
Vol 106 (11) ◽  
pp. 772-778 ◽  
Author(s):  
Helga Manthey ◽  
Alma Zernecke
Keyword(s):  
Dendritic Cells ◽  
Immune Responses ◽  
Cholesterol Homeostasis ◽  
Adaptive Immune Responses ◽  
Adaptive Immune ◽  
Vaccination Strategies ◽  
Atherosclerotic Lesions ◽  
Experimental Approaches ◽  
Lesion Growth ◽  
Progression Of Atherosclerosis

SummaryChronic inflammation drives the development of atherosclerosis. Dendritic cells (DCs) are known as central mediators of adaptive immune responses and the development of immunological memory and tolerance. DCs are present in non-diseased arteries, and accumulate within atherosclerotic lesions where they can be localised in close vicinity to T cells. Recent work has revealed important functions of DCs in regulating immune mechanisms in atherogenesis, and vaccination strategies using DCs have been explored for treatment of disease. However, in line with a phenotypical and functional overlap with plaque macrophages vascular DCs were also identified to engulf lipids, thus contributing to lipid burden in the vessel wall and initiation of lesion growth. Furthermore, a function of DCs in regulating cholesterol homeostasis has been revealed. Finally, phenotypically distinct plasmacytoid dendritic cells (pDCs) have been identified within atherosclerotic lesions. This review will dissect the multifaceted contribution of DCs and pDCs to the initiation and progression of atherosclerosis and the experimental approaches utilising DCs in therapeutic vaccination strategies.

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