scholarly journals Tumors and the danger model.

2002 ◽  
Vol 49 (2) ◽  
pp. 295-302 ◽  
Author(s):  
Dariusz W Kowalczyk
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Dendritic Cells ◽  
Immune Responses ◽  
Antigen Presentation ◽  
Tumor Antigens ◽  
Critical Role ◽  
Immune Surveillance ◽  
Tumor Escape ◽  
Principal Mechanism

This article reviews the evidence for the danger model in the context of immune response to tumors and the insufficiency of the immune system to eliminate tumor growth. Despite their potential immunogenicity tumors do not induce significant immune responses which could destroy malignant cells. According to the danger model, the immune surveillance system fails to detect tumor antigens because transformed cells do not send any danger signals which could activate dendritic cells and initiate an immune response. Instead, tumor cells or antigen presenting cells turn off the responding T cells and induce tolerance. The studies reviewed herein based on model tumor antigens, recombinant viral vectors and detection of tumor specific T cells by MHC/peptide tetramers underscore the critical role of tumor antigen presentation and the context in which it occurs. They indicate that antigen presentation only by activated but not by cancer or resting dendritic cells is necessary for the induction of immune responses to tumor antigens. It becomes apparent that the inability of dendritic cells to become activated provides a biological niche for tumor escape from immune destruction and seems to be a principal mechanism for the failure of tumor immune surveillance.

Development of CD40L-modified tumor small extracellular vesicles for effective induction of antitumor immune response

Nanomedicine ◽  
2020 ◽  
Vol 15 (17) ◽  
pp. 1641-1652
Author(s):  
Wen Liu ◽  
Yuki Takahashi ◽  
Masaki Morishita ◽  
Makiya Nishikawa ◽  
Yoshinobu Takakura
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Dendritic Cells ◽  
Immune Responses ◽  
Antigen Presentation ◽  
Extracellular Vesicles ◽  
Tumor Antigen ◽  
Tumor Antigens ◽  
Cd40 Ligand ◽  
Further Development

Aim: Tumor-derived small extracellular vesicles (TEVs) are considered for use in inducing tumor antigen-specific immune responses as they contain tumor antigens. The delivery of tumor antigens to the antigen presentation cells (especially dendritic cells [DCs]), and the activation of DCs are the main challenges of TEV therapy. Materials & methods: TEVs were modified with CD40 ligand (CD40L), which can target CD40 expressed on the surface of DCs and can activate them via CD40L-CD40 interactions. Results: It was found that CD40L-TEVs were efficiently taken up by DCs and also activated them. Moreover, tumor antigens were efficiently presented to the T cells by DCs treated with CD40L-TEVs. Conclusion: This study proved that CD40L-modification of TEVs will be helpful for further development of TEV-based tumor vaccination.

scholarly journals WDFY4 is required for cross-presentation in response to viral and tumor antigens

Science ◽  
2018 ◽  
Vol 362 (6415) ◽  
pp. 694-699 ◽  
Author(s):  
Derek J. Theisen ◽  
Jesse T. Davidson ◽  
Carlos G. Briseño ◽  
Marco Gargaro ◽  
Elvin J. Lauron ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Tumor Antigens ◽  
Critical Role ◽  
Tumor Rejection ◽  
Interleukin 12 ◽  
Cross Presentation ◽  
Histocompatibility Complex ◽  
Crispr Screen

During the process of cross-presentation, viral or tumor-derived antigens are presented to CD8+ T cells by Batf3-dependent CD8α+/XCR1+ classical dendritic cells (cDC1s). We designed a functional CRISPR screen for previously unknown regulators of cross-presentation, and identified the BEACH domain–containing protein WDFY4 as essential for cross-presentation of cell-associated antigens by cDC1s in mice. However, WDFY4 was not required for major histocompatibility complex class II presentation, nor for cross-presentation by monocyte-derived dendritic cells. In contrast to Batf3–/– mice, Wdfy4–/– mice displayed normal lymphoid and nonlymphoid cDC1 populations that produce interleukin-12 and protect against Toxoplasma gondii infection. However, similar to Batf3–/– mice, Wdfy4–/– mice failed to prime virus-specific CD8+ T cells in vivo or induce tumor rejection, revealing a critical role for cross-presentation in antiviral and antitumor immunity.

scholarly journals The Role of Dendritic Cells in TB and HIV Infection

2020 ◽  
Vol 9 (8) ◽  
pp. 2661
Author(s):  
Rachel Abrahem ◽  
Emerald Chiang ◽  
Joseph Haquang ◽  
Amy Nham ◽  
Yu-Sam Ting ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Dendritic Cells ◽  
Dendritic Cell ◽  
Hiv Infection ◽  
Cell Response ◽  
Defense Mechanism ◽  
Critical Role ◽  
Cytokine Release ◽  
T Helper 1

Dendritic cells are the principal antigen-presenting cells (APCs) in the host defense mechanism. An altered dendritic cell response increases the risk of susceptibility of infections, such as Mycobacterium tuberculosis (M. tb), and the survival of the human immunodeficiency virus (HIV). The altered response of dendritic cells leads to decreased activity of T-helper-1 (Th1), Th2, Regulatory T cells (Tregs), and Th17 cells in tuberculosis (TB) infections due to a diminishment of cytokine release from these APCs, while HIV infection leads to DC maturation, allowing DCs to migrate to lymph nodes and the sub-mucosa where they then transfer HIV to CD4 T cells, although there is controversy around this topic. Increases in the levels of the antioxidant glutathione (GSH) plays a critical role in maintaining dendritic cell redox homeostasis, leading to an adequate immune response with sufficient cytokine release and a subsequent robust immune response. Thus, an understanding of the intricate pathways involved in the dendritic cell response are needed to prevent co-infections and co-morbidities in individuals with TB and HIV.

scholarly journals Natural Killer Dendritic Cells Enhance Immune Responses Elicited byα-Galactosylceramide-Stimulated Natural Killer T Cells

2013 ◽  
Vol 2013 ◽  
pp. 1-18 ◽  
Author(s):  
Sung Won Lee ◽  
Hyun Jung Park ◽  
Nayoung Kim ◽  
Seokmann Hong
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Immune Responses ◽  
Natural Killer ◽  
Immune Cells ◽  
Tumor Antigens ◽  
Nkt Cells ◽  
Innate Immune ◽  
Innate Immune Cells ◽  
Natural Killer T

Natural killer dendritic cells (NKDCs) possess potent anti-tumor activity, but the cellular effect of NKDC interactions with other innate immune cells is unclear. In this study, we demonstrate that the interaction of NKDCs and natural killer T (NKT) cells is required for the anti-tumor immune responses that are elicited byα-galactosylceramide (α-GC) in mice. The rapid and strong expression of interferon-γby NKDCs afterα-GC stimulation was dependent on NKT cells. Various NK and DC molecular markers and cytotoxic molecules were up-regulated followingα-GC administration. This up-regulation could improve NKDC presentation of tumor antigens and increase cytotoxicity against tumor cells. NKDCs were required for the stimulation of DCs, NK cells, and NKT cells. The strong anti-tumor immune responses elicited byα-GC may be due to the down-regulation of regulatory T cells. Furthermore, the depletion of NKDCs dampened the tumor clearance mediated byα-GC-stimulated NKT cellsin vivo. Taken together, these results indicate that complex interactions of innate immune cells might be required to achieve optimal anti-tumor immune responses during the early stages of tumorigenesis.

scholarly journals Crosstalk between Dendritic Cells and Immune Modulatory Agents against Sepsis

Genes ◽  
2020 ◽  
Vol 11 (3) ◽  
pp. 323 ◽  
Author(s):  
Guoying Wang ◽  
Xianghui Li ◽  
Lei Zhang ◽  
Abualgasim Elgaili Abdalla ◽  
Tieshan Teng ◽  
...  
Keyword(s):  
Immune Response ◽  
Dendritic Cells ◽  
Immune Responses ◽  
Critical Role ◽  
Innate Immune ◽  
Adaptive Immune Responses ◽  
Adaptive Immune ◽  
Th2 Responses ◽  
Novel Strategy

Dendritic cells (DCs) play a critical role in the immune system which sense pathogens and present their antigens to prime the adaptive immune responses. As the progression of sepsis occurs, DCs are capable of orchestrating the aberrant innate immune response by sustaining the Th1/Th2 responses that are essential for host survival. Hence, an in-depth understanding of the characteristics of DCs would have a beneficial effect in overcoming the obstacle occurring in sepsis. This paper focuses on the role of DCs in the progression of sepsis and we also discuss the reverse sepsis-induced immunosuppression through manipulating the DC function. In addition, we highlight some potent immunotherapies that could be used as a novel strategy in the early treatment of sepsis.

scholarly journals Immune Response of Indian Preterm Infants to Pentavalent Vaccine Varies With Component Antigens and Gestational Age

2021 ◽  
Vol 12 ◽  
Author(s):  
Archana Kulkarni-Munje ◽  
Nandini Malshe ◽  
Sonali Palkar ◽  
Aniket Amlekar ◽  
Sanjay Lalwani ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Dendritic Cells ◽  
Hepatitis B ◽  
Immune Responses ◽  
Antibody Response ◽  
Preterm Infants ◽  
Gestational Age ◽  
Childhood Vaccination ◽  
Pentavalent Vaccine

Childhood vaccination plays critical role in protecting infants from several dreaded diseases. Of the global 15 million preterm (PT) infants with compromised immune system born annually, India contributes to >3.5 million. Generation of adequate vaccine-induced immune response needs to be ensured of their protection. Immune response of Indian PT (n = 113) and full-term (FT, n = 80) infants to pentavalent vaccine administered as per the national recommendation was studied. Antibody titers against component antigens of pentavalent vaccine, immune cells profiling (T and B cells, monocytes and dendritic cells) and plasma cytokines were determined pre- and post-vaccination. Additionally, cell-mediated recall immune responses to pentavalent antigens were evaluated after short time antigenic exposure to infant PBMCs. Irrespective of gestational age (GA), all the infants developed adequate antibody response against tetanus, diphtheria, and protective but lower antibody levels for Haemophilus influenzae type-b and hepatitis B in preterm infants. Lower (~74%) protective antibody response to pertussis was independent of gestational age. PT-infants exhibited lower frequencies of CD4 T cells/dendritic cells/monocytes, increased plasma IL-10 levels and lower proliferation of central and effector memory T cells than in term-infants. Proliferative central memory response of FT-infants without anti-pertussis antibodies suggests protection from subsequent infection. Responder/non-responder PT-infants lacked immunological memory and could be infected with Bordetella. For hepatitis B, the recall response was gestational age-dependent and antibody status-independent. Humoral/cellular immune responses of PT-infants were dependent on the type of the immunogen. Preterm infants born before 32 weeks of gestation may need an extra dose of pentavalent vaccine for long lived robust immune response.

scholarly journals Modulation of lactate-lysosome axis in dendritic cells by clotrimazole potentiates antitumor immunity

2021 ◽  
Vol 9 (5) ◽  
pp. e002155
Author(s):  
Zining Wang ◽  
Feifei Xu ◽  
Jie Hu ◽  
Hongxia Zhang ◽  
Lei Cui ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
T Cell ◽  
Antigen Presentation ◽  
T Cell Activation ◽  
Therapeutic Efficacy ◽  
Antitumor Immunity ◽  
Critical Role ◽  
T Cell Response

BackgroundDendritic cells (DCs) play a critical role in antitumor immunity, but the therapeutic efficacy of DC-mediated cancer vaccine remains low, partly due to unsustainable DC function in tumor antigen presentation. Thus, identifying drugs that could enhance DC-based antitumor immunity and uncovering the underlying mechanism may provide new therapeutic options for cancer immunotherapy.MethodsIn vitro antigen presentation assay was used for DC-modulating drug screening. The function of DC and T cells was measured by flow cytometry, ELISA, or qPCR. B16, MC38, CT26 tumor models and C57BL/6, Balb/c, nude, and Batf3−/− mice were used to analyze the in vivo therapy efficacy and impact on tumor immune microenvironment by clotrimazole treatment.ResultsBy screening a group of small molecule inhibitors and the US Food and Drug Administration (FDA)-approved drugs, we identified that clotrimazole, an antifungal drug, could promote DC-mediated antigen presentation and enhance T cell response. Mechanistically, clotrimazole acted on hexokinase 2 to regulate lactate metabolic production and enhanced the lysosome pathway and Chop expression in DCs subsequently induced DC maturation and T cell activation. Importantly, in vivo clotrimazole administration induced intratumor immune infiltration and inhibited tumor growth depending on both DCs and CD8+ T cells and potentiated the antitumor efficacy of anti-PD1 antibody.ConclusionsOur findings showed that clotrimazole could trigger DC activation via the lactate-lysosome axis to promote antigen cross-presentation and could be used as a potential combination therapy approach to improving the therapeutic efficacy of anti-PD1 immunotherapy.

scholarly journals Dendritic Cells Can Initiate Protective Immune Responses against Malaria

2001 ◽  
Vol 69 (8) ◽  
pp. 5173-5176 ◽  
Author(s):  
Oscar Bruña-Romero ◽  
Ana Rodriguez
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Immune Responses ◽  
Antigen Presentation ◽  
Plasmodium Yoelii

ABSTRACT An understanding of the antigen presentation mechanisms that mediate induction of protective immune responses against malaria is essential for the development of successful immunization approaches. Here we show that dendritic cells presenting Plasmodium yoelii sporozoite antigens are able to activate specific CD4+ and CD8+ T cells and initiate protective immune responses against malaria in mice.

Dendritic cells regulate T-cell deattachment through the integrin-interacting protein CYTIP

Blood ◽  
2006 ◽  
Vol 107 (3) ◽  
pp. 1003-1009 ◽  
Author(s):  
Susanne Hofer ◽  
Karina Pfeil ◽  
Harald Niederegger ◽  
Susanne Ebner ◽  
Van Anh Nguyen ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Dendritic Cells ◽  
T Cell ◽  
Immune Responses ◽  
Cell Interactions ◽  
Detailed Knowledge ◽  
Active Process ◽  
Interacting Protein ◽  
T Cell Priming

AbstractWhen T cells are primed by dendritic cells (DCs) to initiate antigen-specific immune responses screening for matching antigen receptor-MHC/peptide pairs takes place in DC-T-cell conjugates. For an immune response DC-T-cell conjugates formed during priming events need to dissolve. Although detailed knowledge on molecules involved in the conjugate formation is available, dissolving of them has not been considered to be an active process. Here, we identify CYTIP (cytohesin-interacting protein) to mediate DC-T-cell deattachment. CYTIP, which is induced during maturation of DCs, shortly accumulates to the contact zones with T cells within the first hour of coculture. Specific silencing of CYTIP results in stronger adhesion of DCs to T cells and to fibronectin. When a need for deattachment is created in a T-cell priming assay by only partially loading DCs with antigen, CYTIP silencing causes reduced priming capacity. Thus, CYTIP allows DCs to actively control DC-T-cell interactions.

scholarly journals Dendritic Cells and Their Multiple Roles during Malaria Infection

2016 ◽  
Vol 2016 ◽  
pp. 1-11 ◽  
Author(s):  
Kelly N. S. Amorim ◽  
Daniele C. G. Chagas ◽  
Fernando B. Sulczewski ◽  
Silvia B. Boscardin
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Immune Responses ◽  
Antigen Presentation ◽  
Causative Agent ◽  
Malaria Infection ◽  
Multiple Roles ◽  
Key Factors ◽  
Adaptive Immune Responses ◽  
Adaptive Immune

Dendritic cells (DCs) play a central role in the initiation of adaptive immune responses, efficiently presenting antigens to T cells. This ability relies on the presence of numerous surface and intracellular receptors capable of sensing microbial components as well as inflammation and on a very efficient machinery for antigen presentation. In this way, DCs sense the presence of a myriad of pathogens, includingPlasmodiumspp., the causative agent of malaria. Despite many efforts to control this infection, malaria is still responsible for high rates of morbidity and mortality. Different groups have shown that DCs act duringPlasmodiuminfection, and data suggest that the phenotypically distinct DCs subsets are key factors in the regulation of immunity during infection. In this review, we will discuss the importance of DCs for the induction of immunity against the different stages ofPlasmodium, the outcomes of DCs activation, and also what is currently known aboutPlasmodiumcomponents that trigger such activation.

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