scholarly journals Dendritic Cells The Tumor Microenvironment and the Challenges for an Effective Antitumor Vaccination

2012 ◽  
Vol 2012 ◽  
pp. 1-15 ◽  
Author(s):  
Fabian Benencia ◽  
Leslee Sprague ◽  
John McGinty ◽  
Michelle Pate ◽  
Maria Muccioli
Keyword(s):  
Clinical Trials ◽  
Dendritic Cells ◽  
Tumor Microenvironment ◽  
Immune Responses ◽  
Immune Cells ◽  
Therapeutic Potential ◽  
Human Cancer ◽  
Dc Vaccines ◽  
Tumor Clearance ◽  
Antigen Presenting

Many clinical trials have been carried out or are in progress to assess the therapeutic potential of dendritic-cell- (DC-) based vaccines on cancer patients, and recently the first DC-based vaccine for human cancer was approved by the FDA. Herewith, we describe the general characteristics of DCs and different strategies to generate effective antitumor DC vaccines. In recent years, the relevance of the tumor microenvironment in the progression of cancer has been highlighted. It has been shown that the tumor microenvironment is capable of inactivating various components of the immune system responsible for tumor clearance. In particular, the effect of the tumor microenvironment on antigen-presenting cells, such as DCs, does not only render these immune cells unable to induce specific immune responses, but also turns them into promoters of tumor growth. We also describe strategies likely to increase the efficacy of DC vaccines by reprogramming the immunosuppressive nature of the tumor microenvironment.

scholarly journals Tolerogenic Dendritic Cells on Transplantation: Immunotherapy Based on Second Signal Blockage

2015 ◽  
Vol 2015 ◽  
pp. 1-15 ◽  
Author(s):  
Priscila de Matos Silva ◽  
Julia Bier ◽  
Lisiery Negrini Paiatto ◽  
Cassia Galdino Albuquerque ◽  
Caique Lopes Souza ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Dendritic Cells ◽  
Immune Responses ◽  
Immunological Synapse ◽  
Ex Vivo ◽  
Transplant Rejection ◽  
Innate And Adaptive Immunity ◽  
Tolerogenic Dendritic Cells ◽  
Current Therapies ◽  
Antigen Presenting

Dendritic cells (DCs), the most important professional antigen-presenting cells (APC), play crucial role in both immunity and tolerance. It is well known that DCs are able to mount immune responses against foreign antigens and simultaneously tolerate self-antigens. Since DCs can be modulated depending on the surrounding microenvironment, they can act as a bridge between innate and adaptive immunity. However, the mechanisms that support this dual role are not entirely clear. Recent studies have shown that DCs can be manipulatedex vivoin order to trigger their tolerogenic profile, what can be a tool to be used in clinical trials aiming the treatment of various diseases and the prevention of transplant rejection. In this sense, the blockage of costimulatory molecules on DC, in the attempt of inhibiting the second signal in the immunological synapse, can be considered as one of the main strategies under development. This review brings an update on current therapies using tolerogenic dendritic cells modulated with costimulatory blockers with the aim of reducing transplant rejection. However, although there are current clinical trials using tolerogenic DC to treat allograft rejection, the actual challenge is to modulate these cells in order to maintain a permanent tolerogenic profile.

scholarly journals Network and systems based re-engineering of dendritic cells with non-coding RNAs for cancer immunotherapy

2020 ◽  
Author(s):  
Xin Lai ◽  
Florian S. Dreyer ◽  
Martina Cantone ◽  
Martin Eberhardt ◽  
Kerstin F. Gerer ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Immune Responses ◽  
Rna Sequencing ◽  
Therapeutic Potential ◽  
Mirna Gene ◽  
Sequencing Data ◽  
Dc Optimization ◽  
Signalling Network ◽  
Differentially Expressed Mirnas ◽  
Antigen Presenting

AbstractDendritic cells (DCs) are professional antigen-presenting cells that induce and regulate adaptive immunity by presenting antigens to T cells. Due to their coordinative role in adaptive immune responses, DCs have been used as cell-based therapeutic vaccination against cancer. The capacity of DCs to induce a therapeutic immune response can be enhanced by re-wiring of cellular signalling pathways with microRNAs (miRNAs). Since the activation and maturation of DCs is controlled by an interconnected signalling network, we deploy an approach that combines RNA sequencing data and systems biology methods to delineate miRNA-based strategies that enhance DC-elicited immune responses.Through RNA sequencing of IKKβ-matured DCs that are currently being tested in a clinical trial on therapeutic anti-cancer vaccination, we identified 44 differentially expressed miRNAs. According to a network analysis, most of these miRNAs regulate targets that are linked to immune pathways, such as cytokine and interleukin signalling. We employed a network topology-oriented scoring model to rank the miRNAs, analysed their impact on immunogenic potency of DCs, and identified dozens of promising miRNA candidates with miR-15a and miR-16 as the top ones. The results of our analysis are incorporated in a database which constitutes a tool to identify DC-relevant miRNA-gene interactions with therapeutic potential (www.synmirapy.net/dc-optimization).

scholarly journals Terminating Cancer by Blocking VISTA as a Novel Immunotherapy: Hasta la vista, baby

2021 ◽  
Vol 11 ◽  
Author(s):  
Ji-Eun Irene Yum ◽  
Young-Kwon Hong
Keyword(s):  
Monoclonal Antibody ◽  
Clinical Trials ◽  
T Cells ◽  
Dendritic Cells ◽  
Tumor Microenvironment ◽  
Cancer Progression ◽  
Immune Cells ◽  
Suppressor Cells ◽  
Myeloid Derived Suppressor Cells ◽  
Checkpoint Molecule

VISTA is an up-and-coming immune checkpoint molecule that can become the target of new cancer immunotherapy treatments. Immune cells in the tumor microenvironment can largely influence the progression of cancer through inhibitory and stimulatory pathways. Indeed, VISTA is expressed on many immune cells, including T cells, myeloid-derived suppressor cells, tumor-associated macrophages, and dendritic cells. VISTA has predominantly been shown to act in an immune-suppressing manner that enables cancer progression. This review will delve into results from preclinical murine studies of anti-VISTA monoclonal antibody treatments, bring together recent studies that detect VISTA expression on immune cells from patient tumors of various cancers, and discuss ongoing clinical trials involving VISTA.

scholarly journals Rapamycin Alternatively Modifies Mitochondrial Dynamics in Dendritic Cells to Reduce Kidney Ischemic Reperfusion Injury

2021 ◽  
Vol 22 (10) ◽  
pp. 5386
Author(s):  
Maria Namwanje ◽  
Bijay Bisunke ◽  
Thomas V. Rousselle ◽  
Gene G. Lamanilao ◽  
Venkatadri S. Sunder ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Immune Responses ◽  
Therapeutic Potential ◽  
Ex Vivo ◽  
Mitochondrial Dynamics ◽  
Graft Loss ◽  
Kidney Injury ◽  
Adaptive Immune ◽  
Consumption Rates ◽  
Regulatory Phenotype

Dendritic cells (DCs) are unique immune cells that can link innate and adaptive immune responses and Immunometabolism greatly impacts their phenotype. Rapamycin is a macrolide compound that has immunosuppressant functions and is used to prevent graft loss in kidney transplantation. The current study evaluated the therapeutic potential of ex-vivo rapamycin treated DCs to protect kidneys in a mouse model of acute kidney injury (AKI). For the rapamycin single (S) treatment (Rapa-S-DC), Veh-DCs were treated with rapamycin (10 ng/mL) for 1 h before LPS. In contrast, rapamycin multiple (M) treatment (Rapa-M-DC) were exposed to 3 treatments over 7 days. Only multiple ex-vivo rapamycin treatments of DCs induced a persistent reprogramming of mitochondrial metabolism. These DCs had 18-fold more mitochondria, had almost 4-fold higher oxygen consumption rates, and produced more ATP compared to Veh-DCs (Veh treated control DCs). Pathway analysis showed IL10 signaling as a major contributing pathway to the altered immunophenotype after Rapamycin treatment compared to vehicle with significantly lower cytokines Tnfa, Il1b, and Il6, while regulators of mitochondrial content Pgc1a, Tfam, and Ho1 remained elevated. Critically, adoptive transfer of rapamycin-treated DCs to WT recipients 24 h before bilateral kidney ischemia significantly protected the kidneys from injury with a significant 3-fold improvement in kidney function. Last, the infusion of DCs containing higher mitochondria numbers (treated ex-vivo with healthy isolated mitochondria (10 µg/mL) one day before) also partially protected the kidneys from IRI. These studies demonstrate that pre-emptive infusion of ex-vivo reprogrammed DCs that have higher mitochondria content has therapeutic capacity to induce an anti-inflammatory regulatory phenotype to protect kidneys from injury.

Functional domains of HSP70 stimulate generation of cytokines and chemokines, maturation of dendritic cells and adjuvanticity

2004 ◽  
Vol 32 (4) ◽  
pp. 629-632 ◽  
Author(s):  
T. Lehner ◽  
Y. Wang ◽  
T. Whittall ◽  
E. McGowan ◽  
C.G. Kelly ◽  
...  
Keyword(s):  
Amino Acids ◽  
Dendritic Cells ◽  
Immune Responses ◽  
Cd40 Ligand ◽  
Interleukin 12 ◽  
Cytokines And Chemokines ◽  
Cc Chemokines ◽  
Factor Α ◽  
Antigen Presenting ◽  
Necrosis Factor

Microbial HSP70 (heat-shock protein 70) consists of three functionally distinct domains: an N-terminal 44 kDa ATPase portion (amino acids 1–358), followed by an 18 kDa peptide-binding domain (amino acids 359–494) and a C-terminal 10 kDa fragment (amino acids 495–609). Immunological functions of these three different domains in stimulating monocytes and dendritic cells have not been fully defined. However, the C-terminal portion (amino acids 359–610) stimulates the production of CC chemokines, IL-12 (interleukin-12), TNFα(tumour necrosis factor α), NO and maturation of dendritic cells and also functions as an adjuvant in the induction of immune responses. In contrast, the ATPase domain of microbial HSP70 mostly lacks these functions. Since the receptor for HSP70 is CD40, which with its CD40 ligand constitutes a major co-stimulatory pathway in the interaction between antigen-presenting cells and T-cells, HSP70 may function as an alternative ligand to CD40L. HSP70–CD40 interaction has been demonstrated in non-human primates to play a role in HIV infection, in protection against Mycobacterium tuberculosis and in conversion of tolerance to immunity.

scholarly journals Regulation of the Migration of Distinct Dendritic Cell Subsets

2021 ◽  
Vol 9 ◽  
Author(s):  
Meng Feng ◽  
Shuping Zhou ◽  
Yong Yu ◽  
Qinghong Su ◽  
Xiaofan Li ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Dendritic Cell ◽  
Immune Responses ◽  
The Body ◽  
Inflammatory Factors ◽  
Pathogenic Microorganisms ◽  
Migration Patterns ◽  
Dendritic Cell Subsets ◽  
And Migration ◽  
Antigen Presenting

Dendritic cells (DCs), a class of antigen-presenting cells, are widely present in tissues and apparatuses of the body, and their ability to migrate is key for the initiation of immune activation and tolerogenic immune responses. The importance of DCs migration for their differentiation, phenotypic states, and immunologic functions has attracted widespread attention. In this review, we discussed and compared the chemokines, membrane molecules, and migration patterns of conventional DCs, plasmocytoid DCs, and recently proposed DC subgroups. We also review the promoters and inhibitors that affect DCs migration, including the hypoxia microenvironment, tumor microenvironment, inflammatory factors, and pathogenic microorganisms. Further understanding of the migration mechanisms and regulatory factors of DC subgroups provides new insights for the treatment of diseases, such as infection, tumors, and vaccine preparation.

scholarly journals Natural Killer Cells and Dendritic Cells: Expanding Clinical Relevance in the Non-Small Cell Lung Cancer (NSCLC) Tumor Microenvironment

Cancers ◽  
2021 ◽  
Vol 13 (16) ◽  
pp. 4037
Author(s):  
Pankaj Ahluwalia ◽  
Meenakshi Ahluwalia ◽  
Ashis K. Mondal ◽  
Nikhil S. Sahajpal ◽  
Vamsi Kota ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Dendritic Cells ◽  
Tumor Microenvironment ◽  
Small Cell Lung Cancer ◽  
Nk Cells ◽  
Natural Killer ◽  
Cell Lung Cancer ◽  
Immune Cells ◽  
Small Cell ◽  
Small Cell Lung

Non-small cell lung cancer (NSCLC) is a major subtype of lung cancer that accounts for almost 85% of lung cancer cases worldwide. Although recent advances in chemotherapy, radiotherapy, and immunotherapy have helped in the clinical management of these patients, the survival rate in advanced stages remains dismal. Furthermore, there is a critical lack of accurate prognostic and stratification markers for emerging immunotherapies. To harness immune response modalities for therapeutic benefits, a detailed understanding of the immune cells in the complex tumor microenvironment (TME) is required. Among the diverse immune cells, natural killer (NK cells) and dendritic cells (DCs) have generated tremendous interest in the scientific community. NK cells play a critical role in tumor immunosurveillance by directly killing malignant cells. DCs link innate and adaptive immune systems by cross-presenting the antigens to T cells. The presence of an immunosuppressive milieu in tumors can lead to inactivation and poor functioning of NK cells and DCs, which results in an adverse outcome for many cancer patients, including those with NSCLC. Recently, clinical intervention using modified NK cells and DCs have shown encouraging response in advanced NSCLC patients. Herein, we will discuss prognostic and predictive aspects of NK cells and DC cells with an emphasis on NSCLC. Additionally, the discussion will extend to potential strategies that seek to enhance the anti-tumor functionality of NK cells and DCs.

scholarly journals Targeting regulatory T cells for immunotherapy in melanoma

2021 ◽  
Vol 2 (1) ◽  
Author(s):  
Lili Huang ◽  
Yeye Guo ◽  
Shujing Liu ◽  
Huaishan Wang ◽  
Jinjin Zhu ◽  
...  
Keyword(s):  
T Cells ◽  
Tumor Microenvironment ◽  
Regulatory T Cells ◽  
Immune Responses ◽  
Immune Cells ◽  
Therapeutic Efficacy ◽  
Patient Survival ◽  
Therapeutic Antibodies ◽  
Promising Strategy ◽  
Fine Tune

AbstractRegulatory T cells (Tregs) are essential in the maintenance of immunity, and they are also a key to immune suppressive microenvironment in solid tumors. Many studies have revealed the biology of Tregs in various human pathologies. Here we review recent understandings of the immunophenotypes and suppressive functions of Tregs in melanoma, including Treg recruitment and expansion in a tumor. Tregs are frequently accumulated in melanoma and the ratio of CD8+ T cells versus Tregs in the melanoma is predictive for patient survival. Hence, depletion of Tregs is a promising strategy for the enhancement of anti-melanoma immunity. Many recent studies are aimed to target Tregs in melanoma. Distinguishing Tregs from other immune cells and understanding the function of different subsets of Tregs may contribute to better therapeutic efficacy. Depletion of functional Tregs from the tumor microenvironment has been tested to induce clinically relevant immune responses against melanomas. However, the lack of Treg specific therapeutic antibodies or Treg specific depleting strategies is a big hurdle that is yet to be overcome. Additional studies to fine-tune currently available therapies and more agents that specifically and selectively target tumor infiltrating Tregs in melanoma are urgently needed.

scholarly journals Evaluation of Feline Monocyte-Derived Dendritic Cells Loaded with Internally Inactivated Virus as a Vaccine against Feline Immunodeficiency Virus

2008 ◽  
Vol 15 (3) ◽  
pp. 452-459 ◽  
Author(s):  
Giulia Freer ◽  
Donatella Matteucci ◽  
Paola Mazzetti ◽  
Francesca Tarabella ◽  
Valentina Catalucci ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Immune Responses ◽  
Immune Functions ◽  
Peripheral Blood Mononuclear ◽  
Challenge Virus ◽  
Homologous Virus ◽  
Antibody Titers ◽  
Cellular Immune ◽  
Antigen Presenting

ABSTRACT Dendritic cells are the only antigen-presenting cells that can present exogenous antigens to both helper and cytolytic T cells and prime Th1-type or Th2-type cellular immune responses. Given their unique immune functions, dendritic cells are considered attractive “live adjuvants” for vaccination and immunotherapy against cancer and infectious diseases. The present study was carried out to assess whether the reinjection of autologous monocyte-derived dendritic cells loaded with an aldithriol-2-inactivated primary isolate of feline immune deficiency virus (FIV) was able to elicit protective immune responses against the homologous virus in naive cats. Vaccine efficacy was assessed by monitoring immune responses and, finally, by challenge with the homologous virus of vaccinated, mock-vaccinated, and healthy cats. The outcome of challenge was followed by measuring cellular and antibody responses and viral and proviral loads and quantitating FIV by isolation and a count of CD4+/CD8+ T cells in blood. Vaccinated animals exhibited clearly evident FIV-specific peripheral blood mononuclear cell proliferation and antibody titers in response to immunization; however, they became infected with the challenge virus at rates comparable to those of control animals.

Abstract P219: Losartan Prevents The Recruitment Of Renal M1-like Macrophages And Dendritic Cells In Medulla Of Angiotensin Ii Hypertensive Mice

Hypertension ◽  
2021 ◽  
Vol 78 (Suppl_1) ◽  
Author(s):  
Patricio A Araos ◽  
Andrés Guzmán ◽  
Stefanny M Figueroa ◽  
Javier Reyes ◽  
Cristián A Amador
Keyword(s):  
Dendritic Cells ◽  
Immune Cells ◽  
Renal Cortex ◽  
Renal Medulla ◽  
Ang Ii ◽  
Mhc Ii ◽  
Treatment Changes ◽  
Antigen Presenting

Immune cells play a major role in the development and progression of hypertension. Previous studies have shown that antigen presenting cells (APCs), such as macrophages (Mø) and dendritic cells (DCs) are particularly abundant in kidney. However, the relevance of these renal APCs on hypertension and whether their distribution change during the anti-hypertensive treatment remain unknow. We evaluated whether losartan (Los) treatment changes the abundance of APCs in the renal cortex and medulla in Angiotensin (Ang) II-infused mice.Male C57BL/6 mice (8-12wo) were treated with AngII (490ng/Kg/min), AngII+Los (20mg/Kg/day) or Vehicle for 14 days (n=4-6). Systolic blood pressure (SBP) was measured by the tail cuff method, and renal cortex/medulla were isolated for the measurements of: APCs (MHC-II + :CD11c + ), DCs (APCs:F4/80 - :CD64 - /CD103 + for type-1 DCs, or APCs:F4/80 - :CD64 - :CD11b + for type-2 DCs), and M1-like Mø (APCs:F4/80 - :CD64 + :CD11b + ), by flow cytometry.Los treatment prevented the increased SBP (AngII+Los=118.8±6.4 mmHg vs. AngII=158.0±21.1 mmHg; p<0.001), and the APCs recruitment in renal cortex (AngII+Los=23.2±2.7 vs. AngII=36.0±5.9%; p<0.01) and in renal medulla (Veh=16.3±7.7; AngII=26.3±4,7; AngII+Los=14.9±3.3%; p<0.05) induced by AngII. In addition, we observed an increase of DC2 and M1-like Mø recruitments in renal medulla of AngII mice (DC2 Veh =29.0±5.0 vs. DC2 AngII =45.5±7.3%; p<0.05; M1 Veh =44.8±7.5 vs. M1 AngII =58.3±5.3%; p<0.05), which were prevented by Los treatment (DC2 AngII+Los =27.1±6.8%; p<0.05; M1 AngII+Los =47.0±3.5%; p<0.05). Interestingly, we did not observe differences between groups on M1-like Mø, and DC2 populations in renal cortex. However, Los treatment prevented the increase of DC1 on renal cortex (Veh=2.1±1.4; AngII=5.2±2.4; AngII+Los=2.1±0.8%; p<0.05), without differences between groups at medullar level.Our results show that Los treatment has a differential effect on the APCs populations in renal cortex and medulla, suggesting that renal APCs have different participations on hypertension according their microenvironment.Supported by Fondecyt #1201251 and #3201016

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