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Natural killer cell immunotherapy

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https://www.readbyqxmd.com/read/27933717/mass-cytometry-analytical-approaches-reveal-cytokine-induced-changes-in-natural-killer-cells
#1
Elena Vendrame, Julia Fukuyama, Dara M Strauss-Albee, Susan Holmes, Catherine A Blish
BACKGROUND: Natural killer (NK) cells have antiviral and antitumor activity that could be harnessed for the treatment of infections and malignancies. To maintain cell viability and enhance antiviral and antitumor effects, NK cells are frequently treated with cytokines. Here we performed an extensive assessment of the effects of cytokines on the phenotype and function of human NK cells. METHODS: We used cytometry by time-of-flight (CyTOF) to evaluate NK cell repertoire changes after stimulation with interleukin (IL)-2, IL-15 or a combination of IL- 12/IL-15/IL-18...
December 9, 2016: Cytometry. Part B, Clinical Cytometry
https://www.readbyqxmd.com/read/27933061/ncr1-expression-identifies-canine-natural-killer-cell-subsets-with-phenotypic-similarity-to-human-natural-killer-cells
#2
Jennifer A Foltz, Srinivas S Somanchi, Yanwen Yang, Arianexys Aquino-Lopez, Erin E Bishop, Dean A Lee
Canines spontaneously develop many cancers similar to humans - including osteosarcoma, leukemia, and lymphoma - offering the opportunity to study immune therapies in a genetically heterogeneous and immunocompetent environment. However, a lack of antibodies recognizing canine NK cell markers has resulted in suboptimal characterization and unknown purity of NK cell products, hindering the development of canine models of NK cell adoptive immunotherapy. To this end, we generated a novel antibody to canine NCR1 (NKp46), the putative species-wide marker of NK cells, enabling purification of NK cells for further characterization...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/27930550/role-of-immune-cells-in-pancreatic-cancer-from-bench-to-clinical-application-an-updated-review
#3
Jae Hyuck Chang, Yongjian Jiang, Venu G Pillarisetty
BACKGROUND: Pancreatic cancer (PC) remains difficult to treat, despite the recent advances in various anticancer therapies. Immuno-inflammatory response is considered to be a major risk factor for the development of PC in addition to a combination of genetic background and environmental factors. Although patients with PC exhibit evidence of systemic immune dysfunction, the PC microenvironment is replete with immune cells. METHODS: We searched PubMed for all relevant English language articles published up to March 2016...
December 2016: Medicine (Baltimore)
https://www.readbyqxmd.com/read/27917371/hijacker-of-the-antitumor-immune-response-autophagy-is-showing-its-worst-facet
#4
REVIEW
Elodie Viry, Muhammad Zaeem Noman, Tsolère Arakelian, Audrey Lequeux, Salem Chouaib, Guy Berchem, Etienne Moussay, Jérôme Paggetti, Bassam Janji
Macroautophagy (hereafter referred to as autophagy) is a housekeeping process constitutively executed at basal level in all cells to promote cellular homeostasis by regulating organelle and protein turnover. However, autophagy deregulation caused by several stress factors, such as hypoxia, is prevalent in many cancers. It is now well established that autophagy can act as tumor suppressor or tumor promoter depending on tumor type, stage, and genetic context. In developed tumors, autophagy promotes the survival of cancer cells and therefore operates as a cell resistance mechanism...
2016: Frontiers in Oncology
https://www.readbyqxmd.com/read/27913469/can-we-make-a-better-match-or-mismatch-with-kir-genotyping
#5
Rohtesh S Mehta, Katayoun Rezvani
Natural killer (NK) cell function is regulated by a fine balance between numerous activating and inhibitory receptors, of which killer-cell immunoglobulin-like receptors (KIRs) are among the most polymorphic and comprehensively studied. KIRs allow NK cells to recognize downregulation or the absence of HLA class I molecules on target cells (known as missing-self), a phenomenon that is commonly observed in virally infected cells or cancer cells. Because KIR and HLA genes are located on different chromosomes, in an allogeneic environment such as after hematopoietic stem cell transplantation, donor NK cells that express an inhibitory KIR for an HLA class I molecule that is absent on recipient targets (KIR/KIR-ligand mismatch), can recognize and react to this missing self and mediate cytotoxicity...
December 2, 2016: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/27910927/novel-chemoimmunotherapeutic-strategy-for-hepatocellular-carcinoma-based-on-a-genome-wide-association-study
#6
Kaku Goto, Dorcas A Annan, Tomoko Morita, Wenwen Li, Ryosuke Muroyama, Yasuo Matsubara, Sayaka Ito, Ryo Nakagawa, Yasushi Tanoue, Masahisa Jinushi, Naoya Kato
Pharmacotherapeutic options are limited for hepatocellular carcinoma (HCC). Recently, we identified the anti-tumor ligand MHC class I polypeptide-related sequence A (MICA) gene as a susceptibility gene for hepatitis C virus-induced HCC in a genome-wide association study (GWAS). To prove the concept of HCC immunotherapy based on the results of a GWAS, in the present study, we searched for drugs that could restore MICA expression. A screen of the FDA-approved drug library identified the anti-cancer agent vorinostat as the strongest hit, suggesting histone deacetylase inhibitors (HDACis) as potent candidates...
December 2, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27894857/cytokine-induced-memory-like-differentiation-enhances-unlicensed-nk-cell-anti-leukemia-and-fc%C3%AE-riiia-triggered-responses
#7
Julia A Wagner, Melissa M Berrien-Elliott, Maximillian Rosario, Jeffrey W Leong, Brea A Jewell, Timothy Schappe, Sara Abdel-Latif, Todd A Fehniger
Cytokine-induced memory-like natural killer (NK) cells differentiate following short-term pre-activation with interleukin (IL)-12, IL-15, and IL-18 and display enhanced effector function in response to cytokines or tumor targets for weeks following the initial pre-activation. Conventional NK cell function is dependent upon a licensing signal, classically delivered by an inhibitory receptor engaging its cognate MHC class I ligand. How licensing status integrates with cytokine-induced memory-like NK cell responses is unknown...
November 25, 2016: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/27891129/immunological-and-translational-aspects-of-nk-cell-based-antitumor-immunotherapies
#8
REVIEW
Maxim Shevtsov, Gabriele Multhoff
Natural killer (NK) cells play a pivotal role in the first line of defense against cancer. NK cells that are deficient in CD3 and a clonal T cell receptor (TCR) can be subdivided into two major subtypes, CD56(dim)CD16(+) cytotoxic and CD56(bright)CD16(-) immunoregulatory NK cells. Cytotoxic NK cells not only directly kill tumor cells without previous stimulation by cytotoxic effector molecules, such as perforin and granzymes or via death receptor interactions, but also act as regulatory cells for the immune system by secreting cytokines and chemokines...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/27888293/cytokine-induced-killer-cells-hunt-individual-cancer-cells-in-droves-in-a-mouse-model
#9
Ji Sung Kim, Yong Guk Kim, Hong Kyung Lee, Eun Jae Park, Boyeong Kim, Jong Soon Kang, Heesoon Lee, Youngsoo Kim, Jin Tae Hong, Sang-Bae Han
Cytotoxicity of cytokine-induced killer (CIK) cells depends mainly on their encounters with target cells, but how many CIK cells are required to kill an individual cancer cell is unknown. Here we used time-lapse imaging to quantify the critical effector cell number required to kill an individual target cell. CIK cells killed MHC-I-negative and MHC-I-positive cancer cells, but natural killer (NK) cells destroyed MHC-I-negative cells only. The average threshold number of CIK cells required to kill an individual cancer cell was 6...
November 25, 2016: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/27887866/continuously-expanding-car-nk-92-cells-display-selective-cytotoxicity-against-b-cell-leukemia-and-lymphoma
#10
Sarah Oelsner, Miriam E Friede, Congcong Zhang, Juliane Wagner, Susanne Badura, Peter Bader, Evelyn Ullrich, Oliver G Ottmann, Hans Klingemann, Torsten Tonn, Winfried S Wels
BACKGROUND AIMS: Natural killer (NK) cells can rapidly respond to transformed and stressed cells and represent an important effector cell type for adoptive immunotherapy. In addition to donor-derived primary NK cells, continuously expanding cytotoxic cell lines such as NK-92 are being developed for clinical applications. METHODS: To enhance their therapeutic utility for the treatment of B-cell malignancies, we engineered NK-92 cells by lentiviral gene transfer to express chimeric antigen receptors (CARs) that target CD19 and contain human CD3ζ (CAR 63...
November 22, 2016: Cytotherapy
https://www.readbyqxmd.com/read/27875974/nanoparticle-systems-modulating-myeloid-derived-suppressor-cells-for-cancer-immunotherapy
#11
Avia Wilkerson, Julian Kim, Alex Y Huang, Mei Zhang
Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of immature myeloid cells that are preferentially expanded in cancer. They arise from myeloid progenitor cells that do not differentiate into mature dendritic cells (DCs), granulocytes, or macrophages, and are rather thought to play a pivotal role in immune escape and cancer progression. MDSCs are characterized by the ability to suppress T cell proliferation and cytotoxicity, inhibit natural killer T (NKT) cell activation, and induce the differentiation and expansion of regulatory T cells (Treg)...
November 22, 2016: Current Topics in Medicinal Chemistry
https://www.readbyqxmd.com/read/27870103/role-of-immunotherapy-in-targeting-the-bone-marrow-microenvironment-in-multiple-myeloma-an-evolving-therapeutic-strategy
#12
Clement Chung
Multiple myeloma (referred to henceforth as myeloma) is a B-cell malignancy characterized by unregulated growth of plasma cells in the bone marrow. The treatment paradigm for myeloma underwent significant evolution in the last decade, with an improved understanding of the pathogenesis of the disease as well as the development of therapeutic agents that target not only the tumor cells but also their microenvironment. Despite these therapeutic advances, the prognosis of patients with relapsed or refractory myeloma remains poor...
November 21, 2016: Pharmacotherapy
https://www.readbyqxmd.com/read/27869649/randomized-trial-of-calcipotriol-combined-with-5-fluorouracil-for-skin-cancer-precursor-immunotherapy
#13
Trevor J Cunningham, Mary Tabacchi, Jean-Pierre Eliane, Sara Moradi Tuchayi, Sindhu Manivasagam, Hengameh Mirzaalian, Ahu Turkoz, Raphael Kopan, Andras Schaffer, Arturo P Saavedra, Michael Wallendorf, Lynn A Cornelius, Shadmehr Demehri
BACKGROUND: Actinic keratosis is a precursor to cutaneous squamous cell carcinoma. Long treatment durations and severe side effects have limited the efficacy of current actinic keratosis treatments. Thymic stromal lymphopoietin (TSLP) is an epithelium-derived cytokine that induces a robust antitumor immunity in barrier-defective skin. Here, we investigated the efficacy of calcipotriol, a topical TSLP inducer, in combination with 5-fluorouracil (5-FU) as an immunotherapy for actinic keratosis...
November 21, 2016: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/27853652/human-blood-myeloid-and-plasmacytoid-dendritic-cells-cross-activate-each-other-and-synergize-in-inducing-nk-cell-cytotoxicity
#14
Jasper J P van Beek, Mark A J Gorris, Annette E Sköld, Ibrahim Hatipoglu, Heleen H Van Acker, Evelien L Smits, I Jolanda M de Vries, Ghaith Bakdash
Human blood dendritic cells (DCs) hold great potential for use in anticancer immunotherapies. CD1c(+) myeloid DCs and plasmacytoid DCs (pDCs) have been successfully utilized in clinical vaccination trials against melanoma. We hypothesize that combining both DC subsets in a single vaccine can further improve vaccine efficacy. Here, we have determined the potential synergy between the two subsets in vitro on the level of maturation, cytokine expression, and effector cell induction. Toll-like receptor (TLR) stimulation of CD1c(+) DCs induced cross-activation of immature pDCs and vice versa...
2016: Oncoimmunology
https://www.readbyqxmd.com/read/27835762/il-15-signaling-in-nk-cell-cancer-immunotherapy
#15
REVIEW
Jai Rautela, Nicholas D Huntington
While cancer has been traditionally treated by chemotherapy, radiation, targeted therapies and surgery, a fifth pillar of cancer treatment, immunotherapy, has emerged over the past 10 years and revolutionized our war on cancer. The benchmark for drugs in this category has been set by the development of CD8 T cell checkpoint (CTLA-4 and PD-1/PD-L1) inhibitors. These therapies effectively expand and reactivate the pool of tumor-specific T cells leading to objective response rates of up to 50% in patients with certain cancers...
November 8, 2016: Current Opinion in Immunology
https://www.readbyqxmd.com/read/27834580/nkg2d-ligand-expression-in-pediatric-brain-tumors
#16
Kristen Haberthur, Kathryn Brennan, Virginia Hoglund, Stephanie Balcaitis, Harrison Chinn, Amira Davis, Shannon Kreuser, Conrad Winter, Sarah E S Leary, Gail H Deutsch, Richard G Ellenbogen, Courtney A Crane
Adult brain tumors establish an immunosuppressive tumor microenvironment as a modality of immune escape, with several immunotherapies designed to overcome this barrier. However, the relationship between tumor cells and immune cells in pediatric brain tumor patients is not as well-defined. In this study, we sought to determine whether the model of immune escape observed in adult brain tumors is reflected in patients with pediatric brain tumors by evaluating NKG2D ligand expression on tissue microarrays created from patients with a variety of childhood brain tumor diagnoses, and infiltration of Natural Killer and myeloid cells...
November 11, 2016: Cancer Biology & Therapy
https://www.readbyqxmd.com/read/27831501/characterizing-cd137-upregulation-on-nk-cells-in-patients-receiving-monoclonal-antibody-therapy
#17
A Makkouk, V Sundaram, C Chester, S Chang, A D Colevas, J B Sunwoo, H Maecker, M Desai, H E Kohrt
BACKGROUND: In the era of personalized cancer medicine, identifying techniques for effectively matching patients to efficacious treatments is a critical step in the treatment process. The advent of anti-cancer immunotherapies necessitates novel approaches to biomarker identification beyond traditional genomic profiling. One promising approach is incorporation of nomograms into treatment decisions. Nomograms are prediction tools, based on statistical modeling, designed to predict treatment outcomes...
November 9, 2016: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/27826123/novel-strategies-of-adoptive-immunotherapy-how-natural-killer-cells-may-change-the-treatment-of-elderly-patients-with-acute-myeloblastic-leukemia
#18
REVIEW
Roberto M Lemoli, Sarah Parisi, Antonio Curti
Although many attempts have been made to identify novel molecular-targeted therapies for patients with acute myeloid leukemia, their translation into the clinic have had limited impact. In particular, the question of effective and curative treatments for elderly patients, who are not eligible for stem cell transplantation, remains an unmet medical need. To answer this question, a wide range of immunologic therapeutic strategies, mostly T cell based, have been proposed and investigated. At present, however, the clinical results have been largely unsatisfactory...
November 5, 2016: Experimental Hematology
https://www.readbyqxmd.com/read/27821119/insufficient-natural-killer-cell-responses-against-retroviruses-how-to-improve-nk-cell-killing-of-retrovirus-infected-cells
#19
REVIEW
Elisabeth Littwitz-Salomon, Ulf Dittmer, Kathrin Sutter
Natural killer (NK) cells belong to the innate immune system and protect against cancers and a variety of viruses including retroviruses by killing transformed or infected cells. They express activating and inhibitory receptors on their cell surface and often become activated after recognizing virus-infected cells. They have diverse antiviral effector functions like the release of cytotoxic granules, cytokine production and antibody dependent cellular cytotoxicity. The importance of NK cell activity in retroviral infections became evident due to the discovery of several viral strategies to escape recognition and elimination by NK cells...
November 8, 2016: Retrovirology
https://www.readbyqxmd.com/read/27819527/tigit-a-novel-therapeutic-target-for-tumor-immunotherapy
#20
Xin-Guang Liu, Ming Hou, Yu Liu
Co-inhibitory and co-stimulatory receptors act in concert to regulate adaptive immune cell function, and the balance of these receptors is essential for the maintenance of immune homeostasis. Tumors constitute highly suppressive microenvironments in which elevated expression of co-inhibitory receptors on tumor-infiltrating lymphocytes (TILs) is often found. Functional blockade of the co-inhibitory receptors such as cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed cell death 1 (PD-1) have yielded encouraging outcomes in tumors, generating substantial interest in seeking for additional co-inhibitory molecules that may act as potential interfering targets...
November 7, 2016: Immunological Investigations
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