scholarly journals Pathogen-Associated Molecular Patterns Induced Crosstalk between Dendritic Cells, T Helper Cells, and Natural Killer Helper Cells Can Improve Dendritic Cell Vaccination

2016 ◽  
Vol 2016 ◽  
pp. 1-12 ◽  
Author(s):  
Tammy Oth ◽  
Joris Vanderlocht ◽  
Catharina H. M. J. Van Elssen ◽  
Gerard M. J. Bos ◽  
Wilfred T. V. Germeraad
Keyword(s):  
Dendritic Cells ◽  
Nk Cells ◽  
Natural Killer ◽  
Specific Pattern ◽  
Dendritic Cell Vaccination ◽  
T Helper ◽  
Cell Responses ◽  
Helper Cells ◽  
Molecular Patterns

A coordinated cellular interplay is of crucial importance in both host defense against pathogens and malignantly transformed cells. The various interactions of Dendritic Cells (DC), Natural Killer (NK) cells, and T helper (Th) cells can be influenced by a variety of pathogen-associated molecular patterns (PAMPs) and will lead to enhanced CD8+effector T cell responses. Specific Pattern Recognition Receptor (PRR) triggering during maturation enables DC to enhance Th1 as well as NK helper cell responses. This effect is correlated with the amount of IL-12p70 released by DC. Activated NK cells are able to amplify the proinflammatory cytokine profile of DC via the release of IFN-γ. The knowledge on how PAMP recognition can modulate the DC is of importance for the design and definition of appropriate therapeutic cancer vaccines. In this review we will discuss the potential role of specific PAMP-matured DC in optimizing therapeutic DC-based vaccines, as some of these DC are efficiently activating Th1, NK cells, and cytotoxic T cells. Moreover, to optimize these vaccines, also the inhibitory effects of tumor-derived suppressive factors, for example, on the NK-DC crosstalk, should be taken into account. Finally, the suppressive role of the tumor microenvironment in vaccination efficacy and some proposals to overcome this by using combination therapies will be described.

scholarly journals An Anti-MICA/B Antibody and IL-15 Rescue Altered NKG2D-Dependent NK Cell Responses in Hepatocellular Carcinoma

Cancers ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 3583
Author(s):  
Stefania Mantovani ◽  
Stefania Varchetta ◽  
Dalila Mele ◽  
Matteo Donadon ◽  
Guido Torzilli ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Nk Cells ◽  
Natural Killer ◽  
Nk Cell ◽  
Protein A ◽  
Ligand Interaction ◽  
Cell Responses ◽  
Hcc Cells

Natural killer (NK) cells play a pivotal role in cancer immune surveillance, and activating the receptor/ligand interaction may contribute to control the development and evolution of hepatocellular carcinoma (HCC). We investigated the role of the natural killer group 2 member D (NKG2D) activating receptor and its ligand, the major histocompatibility complex class I chain-related protein A and B (MICA/B) in patients with cirrhosis and HCC subjected to surgical resection, patients with cirrhosis and no HCC, and healthy donors (HD). The NKG2D-mediated function was determined in peripheral blood (PB), in tumor-infiltrating lymphocytes (NK-TIL), and in matched surrounding liver tissue (NK-LIL). A group of patients treated with sorafenib because of clinically advanced HCC was also studied. A humanized anti-MICA/B monoclonal antibody (mAb) was used in in vitro experiments to examine NK cell-mediated antibody-dependent cellular cytotoxicity. Serum concentrations of soluble MICA/B were evaluated by ELISA. IL-15 stimulation increased NKG2D-dependent activity which, however, remained dysfunctional in PB NK cells from HCC patients, in line with the reduced NKG2D expression on NK cells. NK-TIL showed a lower degranulation ability than NK-LIL, which was restored by IL-15 stimulation. Moreover, in vitro IL-15 stimulation enhanced degranulation and interferon-γ production by PB NK from patients at month one of treatment with sorafenib. Anti-MICA/B mAb associated with IL-15 was able to induce PB NK cytotoxicity for primary HCC cells in HD and patients with HCC, who also showed NK-TIL degranulation for autologous primary HCC cells. Our findings highlight the key role of the NKG2D-MICA/B axis in the regulation of NK cell responses in HCC and provide evidence in support of a potentially important role of anti-MICA/B mAb and IL-15 stimulation in HCC immunotherapy.

B cell lymphomas of C57L/J mice; the role of natural killer cells and T helper cells in lymphoma development and growth

2000 ◽  
Vol 24 (8) ◽  
pp. 705-718 ◽  
Author(s):  
Gregory S Erianne ◽  
Janine Wajchman ◽  
Robert Yauch ◽  
Vincent K Tsiagbe ◽  
Byung S Kim ◽  
...  
Keyword(s):  
Natural Killer Cells ◽  
B Cell ◽  
Natural Killer ◽  
T Helper Cells ◽  
T Helper ◽  
B Cell Lymphomas ◽  
Killer Cells ◽  
Helper Cells

scholarly journals Role of Natural Killer and Dendritic Cell Crosstalk in Immunomodulation by Commensal Bacteria Probiotics

2011 ◽  
Vol 2011 ◽  
pp. 1-10 ◽  
Author(s):  
Valeria Rizzello ◽  
Irene Bonaccorsi ◽  
Maria Luisa Dongarrà ◽  
Lisbeth Nielsen Fink ◽  
Guido Ferlazzo
Keyword(s):  
Dendritic Cells ◽  
Nk Cells ◽  
Natural Killer ◽  
Cross Talk ◽  
Adaptive Immune Response ◽  
Distinct Species ◽  
Commensal Bacteria ◽  
Mucosal Surfaces ◽  
Infected Cells

A cooperative dialogue between natural killer (NK) cells and dendritic cells (DCs) has been elucidated in the last years. They help each other to acquire their complete functions, both in the periphery and in the secondary lymphoid organs. Thus, NK cells' activation by dendritic cells allows the killing of transformed or infected cells in the periphery but may also be important for the generation of adaptive immunity. Indeed, it has been shown that NK cells may play a key role in polarizing a Th1 response upon interaction with DCs exposed to microbial products. This regulatory role of DC/NK cross-talk is of particular importance at mucosal surfaces such as the intestine, where the immune system exists in intimate association with commensal bacteria such as lactic acid bacteria (LAB). We here review NK/DC interactions in the presence of gut-derived commensal bacteria and their role in bacterial strain-dependent immunomodulatory effects. We particularly aim to highlight the ability of distinct species of commensal bacterial probiotics to differently affect the outcome of DC/NK cross-talk and consequently to differently influence the polarization of the adaptive immune response.

Defective killing of dendritic cells by autologous natural killer cells from acute myeloid leukemia patients

Blood ◽  
2005 ◽  
Vol 106 (6) ◽  
pp. 2186-2188 ◽  
Author(s):  
Cyril Fauriat ◽  
Alessandro Moretta ◽  
Daniel Olive ◽  
Régis T. Costello
Keyword(s):  
Acute Myeloid Leukemia ◽  
Dendritic Cells ◽  
Nk Cells ◽  
Natural Killer ◽  
T Lymphocyte ◽  
Myeloid Leukemia ◽  
Ex Vivo ◽  
Lymphocyte Responses ◽  
Acute Myeloid

Abstract At the frontier between innate and adaptive immunity, dendritic cells (DCs) secrete numerous cytokines and express costimulatory molecules that initiate or enhance natural killer (NK) and T-lymphocyte responses. NK cells also regulate DC physiology by killing immature DCs (iDCs), thus limiting inflammation and inappropriate T-lymphocyte tolerization. In a previous study, we have reported that NK cells from acute myeloid leukemia patients (AML-NK cells) have deficient natural cytotoxicity receptor (NCR) expression. Herein, we analyzed the consequences of such a defect regarding the regulatory role of AML-NK cells in DC physiology. We show that NK cells display poor cytolytic capacities against DCs derived from healthy donor monocytes or derived from autologous leukemic blasts. These data point to a novel defect in the regulation of adaptive immune responses initiated by DCs in AML patients. This may lead to specific T-lymphocyte tolerization by spontaneous or ex vivo expanded iDCs expressing leukemia-derived antigens. (Blood. 2005;106: 2186-2188)

Activation of human NK cells by plasmacytoid dendritic cells and its modulation by CD4+ T helper cells and CD4+ CD25hi T regulatory cells

2005 ◽  
Vol 35 (8) ◽  
pp. 2452-2458 ◽  
Author(s):  
Chiara Romagnani ◽  
Mariella Della Chiesa ◽  
Siegfried Kohler ◽  
Beate Moewes ◽  
Andreas Radbruch ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Nk Cells ◽  
T Helper Cells ◽  
T Regulatory Cells ◽  
Plasmacytoid Dendritic Cells ◽  
Regulatory Cells ◽  
T Helper ◽  
Helper Cells

scholarly journals Role of Cross-Talk between IFN-α-Induced Monocyte-Derived Dendritic Cells and NK Cells in Priming CD8+ T Cell Responses against Human Tumor Antigens

2004 ◽  
Vol 172 (9) ◽  
pp. 5363-5370 ◽  
Author(s):  
Diego Tosi ◽  
Roberta Valenti ◽  
Agata Cova ◽  
Gloria Sovena ◽  
Veronica Huber ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
T Cell ◽  
Nk Cells ◽  
Cross Talk ◽  
Tumor Antigens ◽  
Human Tumor ◽  
T Cell Responses ◽  
Cd8 T Cell ◽  
Cell Responses

scholarly journals The m15 Locus of Murine Cytomegalovirus Modulates Natural Killer Cell Responses to Promote Dissemination to the Salivary Glands and Viral Shedding

Pathogens ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 866
Author(s):  
Baca Chan ◽  
Maja Arapović ◽  
Laura Masters ◽  
Francois Rwandamuiye ◽  
Stipan Jonjić ◽  
...  
Keyword(s):  
Nk Cells ◽  
Salivary Glands ◽  
Natural Killer ◽  
Nk Cell ◽  
Acute Infection ◽  
Killer Cell ◽  
Viral Escape ◽  
Murine Cytomegalovirus ◽  
Viral Shedding ◽  
Cell Responses

As the largest herpesviruses, the 230 kb genomes of cytomegaloviruses (CMVs) have increased our understanding of host immunity and viral escape mechanisms, although many of the annotated genes remain as yet uncharacterised. Here we identify the m15 locus of murine CMV (MCMV) as a viral modulator of natural killer (NK) cell immunity. We show that, rather than discrete transcripts from the m14, m15 and m16 genes as annotated, there are five 3′-coterminal transcripts expressed over this region, all utilising a consensus polyA tail at the end of the m16 gene. Functional inactivation of any one of these genes had no measurable impact on viral replication. However, disruption of all five transcripts led to significantly attenuated dissemination to, and replication in, the salivary glands of multiple strains of mice, but normal growth during acute infection. Disruption of the m15 locus was associated with heightened NK cell responses, including enhanced proliferation and IFNγ production. Depletion of NK cells, but not T cells, rescued salivary gland replication and viral shedding. These data demonstrate the identification of multiple transcripts expressed by a single locus which modulate, perhaps in a concerted fashion, the function of anti-viral NK cells.

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