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https://www.readbyqxmd.com/read/28934563/hemophagocytic-lymphohistiocytosis
#1
Hanny Al-Samkari, Nancy Berliner
Hemophagocytic lymphohistiocytosis is a life-threatening disorder characterized by unbridled activation of cytotoxic T lymphocytes, natural killer (NK) cells, and macrophages resulting in hypercytokinemia and immunemediated injury of multiple organ systems. It is seen in both children and adults and is recognized as primary (driven by underlying genetic mutations that abolish critical proteins required for normal function of cytotoxic T cells and NK cells) or secondary (resulting from a malignant, infectious, or autoimmune stimulus without an identifiable underlying genetic trigger)...
September 13, 2017: Annual Review of Pathology
https://www.readbyqxmd.com/read/28932646/reconstitution-of-multifunctional-cd56-low-cd16-low-natural-killer-cell-subset-in-children-with-acute-leukemia-given-%C3%AE-%C3%AE-t-cell-depleted-hla-haploidentical-haematopoietic-stem-cell-transplantation
#2
Stabile Helena, Nisti Paolo, Peruzzi Giovanna, Fionda Cinzia, Pagliara Daria, Pomonia Brescia Letizia, Merli Pietro, Locatelli Franco, Angela Santoni, Angela Gismondi
We recently described the CD56(low)CD16(low) subset of Natural Killer (NK) cells that both mediate cytotoxic activity and produce IFNγ, being more abundant in bone marrow (BM) than in peripheral blood (PB) of pediatric normal subjects. Given the multifunctional properties of this subset, we examined its development and functional recovery in a cohort of children undergoing α/β T-cell depleted HLA-haploidentical haematopoietic stem cell transplantation (HSCT). The results obtained indicate that CD56(low)CD16(low) NK cells are present in both PB and BM already at one month post-HSCT, with an increased frequency in BM of graft recipients as compared with normal subjects...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28932644/romidepsin-alone-or-in-combination-with-anti-cd20-chimeric-antigen-receptor-expanded-natural-killer-cells-targeting-burkitt-lymphoma-in-vitro-and-in-immunodeficient-mice
#3
Yaya Chu, Ashlin Yahr, Brian Huang, Janet Ayello, Matthew Barth, Mitchell S Cairo
Facilitating the development of alternative targeted therapeutic strategies is urgently required to improve outcome or circumvent chemotherapy resistance in children, adolescents, and adults with recurrent/refractory de novo mature B-cell (CD20) non-Hodgkin lymphoma, including Burkitt lymphoma (BL). Romidepsin, a histone deacetylase inhibitor (HDACi), has been used to treat cutaneous T-cell lymphoma. We have demonstrated the significant anti-tumor effect of anti-CD20 chimeric antigen receptor (CAR) modified expanded peripheral blood natural killer (exPBNK) against rituximab-sensitive and -resistant BL...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28932640/co-delivery-of-the-nkt-agonist-%C3%AE-galactosylceramide-and-tumor-antigens-to-cross-priming-dendritic-cells-breaks-tolerance-to-self-antigens-and-promotes-antitumor-responses
#4
Reem Ghinnagow, Julie De Meester, Luis Javier Cruz, Caroline Aspord, Stéphanie Corgnac, Elodie Macho-Fernandez, Daphnée Soulard, Josette Fontaine, Laurence Chaperot, Julie Charles, Fabrice Soncin, Fathia Mami-Chouaib, Joel Plumas, Christelle Faveeuw, François Trottein
Vaccines designed to abrogate the tolerance of tumor self-antigens and amplify cytotoxic CD8(+) T cells (CTLs) have promise for the treatment of cancer. Type I natural killer (NKT) cells have attracted considerable interest in the cancer therapy field. In the current study, we have exploited the unique ability of NKT cells to serve as T-helper cells to license dendritic cells (DCs) for cross priming with the aim to generate efficient CTL antitumor responses. To this end, we designed a nanoparticle-based vaccine to target cross-priming DCs via the Clec9a endocytic pathway...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28932639/soluble-nkg2d-ligands-in-the-ovarian-cancer-microenvironment-are-associated-with-an-adverse-clinical-outcome-and-decreased-memory-effector-t-cells-independent-of-nkg2d-downregulation
#5
Maulik Vyas, Silke Reinartz, Nathalie Hoffmann, Katrin S Reiners, Sonja Lieber, Julia M Jansen, Uwe Wagner, Rolf Müller, Elke Pogge von Strandmann
The immune receptor NKG2D is predominantly expressed on NK cells and T cell subsets and confers anti-tumor activity. According to the current paradigm, immune surveillance is counteracted by soluble ligands shed into the microenvironment, which down-regulate NKG2D receptor expression. Here, we analyzed the clinical significance of the soluble NKG2D ligands sMICA and sULBP2 in the malignancy-associated ascites of ovarian cancer. We show that high levels of sMICA and sULBP2 in ascites were associated with a poor prognosis...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28932638/the-anti-slamf7-antibody-elotuzumab-mediates-nk-cell-activation-through-both-cd16-dependent-and-independent-mechanisms
#6
Tatiana Pazina, Ashley M James, Alexander W MacFarlane, Natalie A Bezman, Karla A Henning, Christine Bee, Robert F Graziano, Michael D Robbins, Adam D Cohen, Kerry S Campbell
Elotuzumab is a humanized therapeutic monoclonal antibody directed to the surface glycoprotein SLAMF7 (CS1, CRACC, CD319), which is highly expressed on multiple myeloma (MM) tumor cells. Improved clinical outcomes have been observed following treatment of MM patients with elotuzumab in combination with lenalidomide or bortezomib. Previous work showed that elotuzumab stimulates NK cell-mediated antibody-dependent cellular cytotoxicity (ADCC), via Fc-domain engagement with FcγRIIIa (CD16). SLAMF7 is also expressed on NK cells, where it can transmit stimulatory signals...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28930684/tumor-derived-mesenchymal-stem-cells-use-distinct-mechanisms-to-block-the-activity-of-natural-killer-cell-subsets
#7
Sabine Galland, Joanna Vuille, Patricia Martin, Igor Letovanec, Anne Caignard, Giulia Fregni, Ivan Stamenkovic
Mesenchymal stem cells (MSCs) display pleiotropic functions, which include secretion of soluble factors with immunosuppressive activity implicated in cancer progression. We compared the immunomodulatory effects on natural killer (NK) cells of paired intratumor (T)- and adjacent non-tumor tissue (N)-derived MSCs from patients with squamous cell lung carcinoma (SCC). We observed that T-MSCs were more strongly immunosuppressive than N-MSCs and affected both NK function and phenotype, as defined by CD56 expression...
September 19, 2017: Cell Reports
https://www.readbyqxmd.com/read/28928840/a-cytokine-signal-inhibitor-for-rheumatoid-arthritis-enhances-cancer-metastasis-via-depletion-of-nk-cells-in-an-experimental-lung-metastasis-mouse-model-of-colon-cancer
#8
Hideki Shimaoka, Shinsuke Takeno, Kenji Maki, Takahide Sasaki, Suguru Hasegawa, Yuichi Yamashita
Current therapy for rheumatoid arthritis (RA) relies on global suppression of the immune response or specific blockade of inflammatory cytokines. However, it is unclear how immunosuppressants affect patients with cancer. Therefore, in the present study, the effect of three biological agents, tofacitinib, anti-mouse IL-6 receptor antibody (MR16-1) and etanercept, which are used for the treatment of RA diseases, on a tumor-bearing mouse model was investigated. The effect of the three agents was examined using a mouse lung-metastasis model with the murine colon 26 cancer cell line...
September 2017: Oncology Letters
https://www.readbyqxmd.com/read/28927610/structure-and-immunomodulatory-activity-of-a-sulfated-agarose-with-pyruvate-and-xylose-substitutes-from-polysiphonia-senticulosa-harvey
#9
Xiaoliang Zhao, Guangling Jiao, Yi Yang, Miaomiao Li, Qinying Li, Xiaojiang Wang, Chao Cai, Guoyun Li, Jiejie Hao, Guangli Yu
A charged and size uniform polysaccharide PS2 was prepared from red seaweed Polysiphonia senticulosa Harvey. Based on nuclear magnetic resonance (NMR), fourier transform infrared (FTIR) spectroscopy, and electrospray ionization collision-induced-dissociation mass spectrometry (ESI-CID-MS(n)) analysis, PS2 was determined to be a novel 6-O-sulfated agarose which was mainly composed of a repeating unit of alternating (1→3)-linked 6-sulfated-β-d-galactose and (1→4)-linked 3,6-anhydro-α-l-galactose in association with small amount of pyruvate substituted on galactose residues and xylose (Xyl) branched at C2 position of 3,6-anhydro-galactose...
November 15, 2017: Carbohydrate Polymers
https://www.readbyqxmd.com/read/28927159/diagnostic-value-of-inflammatory-cell-infiltrates-tumor-stroma-percentage-and-disease-free-survival-in-patients-with-colorectal-cancer
#10
Katarzyna Jakubowska, Wojciech Kisielewski, Luiza Kańczuga-Koda, Mariusz Koda, Waldemar Famulski
The anticancer immune defense mechanism involves humoral and cellular responses. The main effector mechanisms of antitumor responses involve the following: the activity of cytotoxic T cells; the activation of macrophages and neutrophils; the activity of cytokines secreted by T cells; and natural killer cell activity. Selected cell populations are responsible for the stimulation or suppression of the immune system against tumor cells. Therefore, the aim of the present study was to evaluate the location, extent and composition of the cellular inflammatory infiltration of tumors in patients with colorectal cancer (CRC)...
September 2017: Oncology Letters
https://www.readbyqxmd.com/read/28926962/anti-nkg2d-mab-a-new-treatment-for-crohn-s-disease
#11
REVIEW
Kasper Vadstrup, Flemming Bendtsen
Crohn's disease (CD) and ulcerative colitis (UC) are immunologically-mediated, debilitating conditions resulting from destructive inflammation of the gastrointestinal tract. The pathogenesis of IBD is incompletely understood, but is considered to be the result of an abnormal immune response with a wide range of cell types and proteins involved. Natural Killer Group 2D (NKG2D) is an activating receptor constitutively expressed on human Natural Killer (NK), γδ T, mucosal-associated invariant T (MAIT), CD56⁺ T, and CD8⁺ T cells...
September 16, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28926399/natural-killer-cells-in-hiv-1-infection-and-therapy
#12
Joanna Mikulak, Ferdinando Oriolo, Elisa Zaghi, Clara Di Vito, Domenico Mavilio
: Natural killer (NK) cells are important effectors of innate immunity playing a key role in the eradication and clearance of viral infections. Over the recent years, several studies have shown that HIV-1 pathologically changes NK cell homeostasis and hampers their antiviral effector functions. Moreover, high levels of chronic HIV-1 viremia markedly impair those NK cell regulatory features that normally regulate the cross-talks between innate and adaptive immune responses. These pathogenic events take place early in the infection and are associated with a pathologic redistribution of NK cell subsets that includes the expansion of anergic CD56 NK cells with an aberrant repertoire of activating and inhibitory receptors...
September 18, 2017: AIDS
https://www.readbyqxmd.com/read/28923946/immunoreceptor-tyrosine-based-inhibitory-motif-dependent-functions-of-an-mhc-class-i-specific-nk-cell-receptor
#13
Michael D Bern, Diana L Beckman, Takashi Ebihara, Samantha M Taffner, Jennifer Poursine-Laurent, J Michael White, Wayne M Yokoyama
Natural killer (NK) cells express MHC class I (MHC-I)-specific receptors, such as Ly49A, that inhibit killing of cells expressing self-MHC-I. Self-MHC-I also "licenses" NK cells to become responsive to activating stimuli and regulates the surface level of NK-cell inhibitory receptors. However, the mechanisms of action resulting from these interactions of the Ly49s with their MHC-I ligands, particularly in vivo, have been controversial. Definitive studies could be derived from mice with targeted mutations in inhibitory Ly49s, but there are inherent challenges in specifically altering a single gene within a multigene family...
September 18, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28923404/hla-g-coding-region-polymorphism-is-skewed-in-autistic-spectrum-disorders
#14
Franca R Guerini, Elisabetta Bolognesi, Matteo Chiappedi, Enrico Ripamonti, Alessandro Ghezzo, Michela Zanette, Stefano Sotgiu, Maria Martina Mensi, Alessandra Carta, Maria Paola Canevini, Milena Zanzottera, Cristina Agliardi, Andrea S Costa, Umberto Balottin, Mario Clerici
Different isoforms of HLA-G protein are endowed with a differential ability to induce allogenic tolerance during pregnancy. As prenatal immune activation is suggested to play a role in the onset of autistic spectrum disorders (ASD), we evaluated HLA G*01:01-*01:06 allelic polymorphism in a cohort of Italian children affected by ASD (N=111) their mothers (N=81), and their healthy siblings (N=39). DNA sequencing analysis of HLA-G exon 2, 3 and 4 was used to obtain HLA-G allelic frequencies; alleles distribution was compared with that of two control groups of Caucasoid couples of multiparous women and their partners from Brazil and Denmark...
September 15, 2017: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/28921473/the-development-and-diversity-of-ilcs-nk-cells-and-their-relevance-in-health-and-diseases
#15
Yuxia Zhang, Bing Huang
Next to T and B cells, natural killer (NK) cells are the third largest lymphocyte population. They are recently re-categorized as innate lymphocytes (ILCs), which also include ILC1, ILC2, ILC3, and the lymphoid tissue inducer (LTi) cells. Both NK cells and ILC1 cells are designated as group 1 ILCs because they secrete interferon-γ (IFN-γ) and tumor necrosis factor (TNF). However, in contrast to ILC1 and all other ILCs, NK cells possess potent cytolytic functions that resemble cytotoxic T lymphocytes (CTL)...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28921388/immunomodulatory-potential-of-nanocurcumin-based-formulation
#16
Mahendra Kumar Trivedi, Sambhu Charan Mondal, Mayank Gangwar, Snehasis Jana
Vitamins, minerals, and nanocurcumin play a substantial role in various nutraceutical/pharmaceutical formulations that are widely used in therapeutics, cosmetics, and dietary supplements. The current study aimed to investigate the comparative in vitro immunomodulatory effect of a novel nanocurcumin-based formulation with curcumin in LPS-induced cytokine expression, NK cells' activity, and phagocytosis. The proinflammatory cytokines (TNF-α, IL-1β, and MIP-1α) and NK cells' activity were measured in cell supernatants using ELISA assay; however, phagocytosis activity was performed using colorimetric analysis...
September 18, 2017: Inflammopharmacology
https://www.readbyqxmd.com/read/28920951/srebp-controlled-glucose-metabolism-is-essential-for-nk-cell-functional-responses
#17
Nadine Assmann, Katie L O'Brien, Raymond P Donnelly, Lydia Dyck, Vanessa Zaiatz-Bittencourt, Róisín M Loftus, Paul Heinrich, Peter J Oefner, Lydia Lynch, Clair M Gardiner, Katja Dettmer, David K Finlay
Activated natural killer (NK) cells engage in a robust metabolic response that is required for normal effector function. Using genetic, pharmacological and metabolic analyses, we demonstrated an essential role for Srebp transcription factors in cytokine-induced metabolic reprogramming of NK cells that was independent of their conventional role in the control of lipid synthesis. Srebp was required for elevated glycolysis and oxidative phosphorylation and promoted a distinct metabolic pathway configuration in which glucose was metabolized to cytosolic citrate via the citrate-malate shuttle...
September 18, 2017: Nature Immunology
https://www.readbyqxmd.com/read/28920615/the-phenolic-profiles-of-radix-tetrastigma-after-solid-phase-extraction-spe-and-their-antitumor-effects-and-antioxidant-activities-in-h22-tumor-bearing-mice
#18
Yong Sun, Rong Tsao, Fang Chen, Hongyan Li, Han Peng, Li Jiang, Yuhuan Chen, Zeyuan Deng
Radix Tetrastigma (RT), a herbal medicine and functional food in China, showed strong antiproliferative activities in vitro. However, the effects and the underlying mechanism of phenolic-rich extract of RT in H22 tumor-bearing mice are still unknown. Thus, the phenolic profiles and antitumor/antioxidant activities of a solid phase extraction (SPE) semi-purified extract of RT were investigated by a combination of chemical assays, LC-QTOF-MS/LC-QqQ-MS techniques and a tumor-bearing mice model. As a result, the total phenolic/flavonoid contents (TPC/TFC) and 24 individual phenolics were identified and quantified, which showed higher contents than that of crude extract...
September 18, 2017: Food & Function
https://www.readbyqxmd.com/read/28920003/cd226-natural-killer-cells-fail-to-establish-stable-contacts-with-cancer-cells-and-show-impaired-control-of-tumor-metastasis-in-vivo
#19
Ji Sung Kim, Bo Ram Shin, Hong Kyung Lee, Jae Hee Lee, Ki Hun Kim, Jeong Eun Choi, A Young Ji, Jin Tae Hong, Youngsoo Kim, Sang-Bae Han
CD226 is an activating receptor expressed on natural killer (NK) cells, CD8(+) T cells, and other immune cells. Upon binding to its ligands expressed on target cells, CD226 activates intracellular signaling that triggers cytokine production and degranulation in NK cells. However, the role of CD226 in contact dynamics between NK and cancer cells has remained unclear. Our time-lapse images showed that individual wild-type CD226(+) NK cells contacted B16F10 melanoma cells for 23.7 min, but Cd226(-/-) NK cells only for 12...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28920001/zoledronic-acid-inhibits-nfat-and-il-2-signaling-pathways-in-regulatory-t-cells-and-diminishes-their-suppressive-function-in-patients-with-metastatic-cancer
#20
Dhifaf Sarhan, Caroline Leijonhufvud, Shannon Murray, Kristina Witt, Christina Seitz, Majken Wallerius, Hanjing Xie, Anders Ullén, Ulrika Harmenberg, Elisabet Lidbrink, Charlotte Rolny, John Andersson, Andreas Lundqvist
Regulatory T cells (Treg) suppress anti-tumor immune responses and their infiltration in the tumor microenvironment is associated with inferior prognosis in cancer patients. Thus, in order to enhance anti-tumor immune responses, selective depletion of Treg is highly desired. We found that treatment with zoledronic acid (ZA) resulted in a selective decrease in the frequency of Treg that was associated with a significant increase in proliferation of T cells and natural killer (NK) cells in peripheral blood of patients with metastatic cancer...
2017: Oncoimmunology
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