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https://www.readbyqxmd.com/read/29443657/il-2-and-beyond-in-cancer-immunotherapy
#1
John M Wrangle, Alicia Patterson, C Bryce Johnson, Daniel J Neitzke, Shikhar Mehrotra, Chadrick E Denlinger, Chrystal M Paulos, Zihai Li, David J Cole, Mark P Rubinstein
The development of the T- and natural killer (NK) cell growth factor IL-2 has been a sentinel force ushering in the era of immunotherapy in cancer. With the advent of clinical grade recombinant IL-2 in the mid-1980s, oncologists could for the first time directly manipulate lymphocyte populations with systemic therapy. By itself, recombinant IL-2 can induce clinical responses in up to 15% of patients with metastatic cancer or renal cell carcinoma. When administered with adoptively transferred tumor-reactive lymphocytes, IL-2 promotes T cell engraftment and response rates of up to 50% in metastatic melanoma patients...
February 2018: Journal of Interferon & Cytokine Research
https://www.readbyqxmd.com/read/29440510/educated-natural-killer-cells-show-dynamic-movement-of-the-activating-receptor-nkp46-and-confinement-of-the-inhibitory-receptor-ly49a
#2
Elina Staaf, Per Niklas Hedde, Sunitha Bagawath Singh, Joachim Piguet, Enrico Gratton, Sofia Johansson
Educated natural killer (NK) cells have inhibitory receptors specific for self major histocompatibility complex (MHC) class I molecules and kill cancer cells more efficiently than do NK cells that do not have such receptors (hyporesponsive NK cells). The mechanism behind this functional empowerment through education has so far not been fully described. In addition, distinctive phenotypic markers of educated NK cells at the single-cell level are lacking. We developed a refined version of the image mean square displacement (iMSD) method (called iMSD carpet analysis) and used it in combination with single-particle tracking to characterize the dynamics of the activating receptor NKp46 and the inhibitory receptor Ly49A on resting educated versus hyporesponsive murine NK cells...
February 13, 2018: Science Signaling
https://www.readbyqxmd.com/read/29440505/divergent-requirement-of-t-box-transcription-factors-in-effector-and-memory-nk-cells
#3
Sharline Madera, Clair D Geary, Colleen M Lau, Olga Pikovskaya, Steven L Reiner, Joseph C Sun
The T-box transcription factors T-bet and Eomesodermin (Eomes) instruct discrete stages in NK cell development. However, their role in the immune response of mature NK cells against pathogens remains unexplored. We used an inducible deletion system to elucidate the cell-intrinsic role of T-bet and Eomes in mature NK cells during the course of mouse CMV infection. We show both T-bet and Eomes to be necessary for the expansion of virus-specific NK cells, with T-bet upregulation induced by IL-12 signaling and STAT4 binding to a conserved enhancer region upstream of the Tbx21 loci...
February 9, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29439918/short-term-administration-of-recombinant-human-erythropoietin-decreases-b-cell-number-in-human-peripheral-blood
#4
Tomomi Nagashima, Akihiko Yokohama, Kie Nagai, Tetsuhiro Kasamatsu, Nanami Gotoh, Hirono Iriuchishima, Tomomi Sekigami, Takayuki Saitoh, Hiroshi Handa, Norifumi Tsukamoto, Hirokazu Murakami
OBJECTIVES: There are conflicting results on the influence of recombinant human erythropoietin (rHuEPO) administration to lymphocytes, especially to B cells. METHODS: We analyzed peripheral white blood cell (WBC) subsets in patients who received one bolus administration of rHuEPO. 119 autologous blood donors were enrolled in this study. Fourty-nine out of them were treated with rHuEPO. Blood samples were obtained before the first phlebotomy and one week later before the second one...
February 2, 2018: Transfusion and Apheresis Science
https://www.readbyqxmd.com/read/29439673/il-10-nk-and-tgf-%C3%AE-nk-cells-play-negative-regulatory-roles-in-hiv-infection
#5
Yongjun Jiang, Mei Yang, Xiaojuan Sun, Xi Chen, Meichen Ma, Xiaowan Yin, Shi Qian, Zining Zhang, Yajing Fu, Jing Liu, Xiaoxu Han, Junjie Xu, Hong Shang
BACKGROUND: Natural killer (NK) cells play cytotoxic roles by targeting tumor cells or virus infected cells, they also play regulatory roles by secreting cytokines and chemokines. Transforming growth factor (TGF)-β and interleukin (IL)-10 are important immunosuppressive cytokines potentially related to the immune dysregulation that occurs in the infection of human immunodeficiency virus (HIV). NK cells are an important source of TGF-β and a main early producer of IL-10 in response to viral infection...
February 13, 2018: BMC Infectious Diseases
https://www.readbyqxmd.com/read/29439173/nccn-guidelines-insights-t-cell-lymphomas-version-2-2018
#6
Steven M Horwitz, Stephen M Ansell, Weiyun Z Ai, Jeffrey Barnes, Stefan K Barta, Michael Choi, Mark W Clemens, Ahmet Dogan, John P Greer, Ahmad Halwani, Bradley M Haverkos, Richard T Hoppe, Eric Jacobsen, Deepa Jagadeesh, Youn H Kim, Matthew A Lunning, Amitkumar Mehta, Neha Mehta-Shah, Yahurio Oki, Elise A Olsen, Barbara Pro, Saurabh A Rajguru, Satish Shanbhag, Andrei Shustov, Lubomir Sokol, Pallawi Torka, Ryan Wilcox, Basem William, Jasmine Zain, Mary A Dwyer, Hema Sundar
Natural killer (NK)/T-cell lymphomas are a rare and distinct subtype of non-Hodgkin's lymphomas. NK/T-cell lymphomas are predominantly extranodal and most of these are nasal type, often localized to the upper aerodigestive tract. Because extranodal NK/T-cell lymphomas (ENKL) are rare malignancies, randomized trials comparing different regimens have not been conducted to date and standard therapy has not yet been established for these patients. These NCCN Guidelines Insights discuss the recommendations for the diagnosis and management of patients with ENKL as outlined in the NCCN Guidelines for T-Cell Lymphomas...
February 2018: Journal of the National Comprehensive Cancer Network: JNCCN
https://www.readbyqxmd.com/read/29438058/assessment-of-antibody-dependent-cellular-cytotoxicity-by-flow-cytometry
#7
Thomas D Duensing, Susan R Watson
A useful feature of therapeutic antibodies is the ability to kill the cells to which they bind. Antibodies are capable of mediating cell killing in a variety of ways. Apoptosis, complement-mediated mechanisms, and antibody-dependent cellular cytotoxicity (ADCC) are all effects that can be assayed to characterize lead antibody candidates. Extensive, multidose characterizations of a series of candidates can be performed in a short amount of time using assays developed for high-throughput flow cytometry systems...
February 1, 2018: Cold Spring Harbor Protocols
https://www.readbyqxmd.com/read/29437230/lectin-isolated-from-japanese-red-sword-beans-canavalia-gladiata-as-a-potential-cancer-chemopreventive-agent
#8
Satsuki Une, Koji Nonaka, Junich Akiyama
In this study, we investigated the chemical and biological profile of lectin isolated from Japanese red sword beans (Canavalia gladiata; RSBs). RSB lectin was purified using maltamyl-Sepharose 4B and subjected to amino acid composition and partial amino acid sequencing analyses, and evaluated for blood and carbohydrate specificity, mitogenic activity, splenic natural killer (NK) cell activity, and its effect on B16 melanoma cell proliferation, compared with Concanavalin A (Con A). The amino acid composition and sequences of RSB lectin were similar to those of Con A...
February 13, 2018: Journal of Food Science
https://www.readbyqxmd.com/read/29436412/cell-specific-requirements-for-stat-proteins-and-type-i-ifn-receptor-signaling-discretely-regulate-il-24-and-il-10-expression-in-nk-cells-and-macrophages
#9
Djeneba Dabitao, Christian M Hedrich, Fengying Wang, Vimvara Vacharathit, Jay H Bream
Il10 forms a cytokine cluster with Il19 , Il20 , and Il24 in a conserved region of chromosome 1. The latter genes are in the IL-20 subfamily of IL-10-related cytokines and, although they are not as well studied their biologic actions and expression patterns, seem to have little in common with IL-10. IL-24, like IL-10, however, is uniquely expressed in T cells and is a signature gene of the Th2 lineage, which suggests they could be coregulated in certain cell types. Little is known about other cellular sources of IL-24...
February 7, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29435021/long-lasting-memory-of-cellular-immunity-in-a-chronic-myeloid-leukemia-patient-maintains-molecular-response-5-after-cessation-of-dasatinib
#10
Tatsuro Jo, Kazuhiro Noguchi, Shizuka Hayashi, Sadaharu Irie, Risa Hayase, Haruna Shioya, Youhei Kaneko, Kensuke Horio, Jun Taguchi
Tyrosine kinase inhibitors (TKIs), including imatinib, dasatinib and nilotinib are primarily used in the initial treatment of chronic phase (CP)-chronic myeloid leukemia (CML), as CMLs harbor the BCR-ABL fusion product. An increased number of lymphocytes and large granular lymphocytes (LGLs) have been observed in patients treated with dasatinib, but not other TKIs. The LGLs have been reported to be primarily natural killer (NK) cells and cytotoxic T lymphocytes (CTLs). In the present study, a CP-CML patient who has maintained molecular response 5 for >2...
March 2018: Oncology Letters
https://www.readbyqxmd.com/read/29434775/il-25-promotes-th2-bias-by-upregulating-il-4-and-il-10-expression-of-decidual-%C3%AE-%C3%AE-t-cells-in-early-pregnancy
#11
Yuan Zhang, Ying Wang, Ming-Qing Li, Jie Duan, Deng-Xuan Fan, Li-Ping Jin
Decidual immune cells (DICs), consisting of both innate and adaptive immune cells, have a pivotal role in maintaining immune tolerance for normal pregnancy. Our previous study demonstrated that interleukin (IL)-25 stimulates the proliferation of decidual stromal cells (DSCs) in an autocrine manner. However, the role of IL-25 in functional regulation of DICs is largely unknown. Flow cytometry was used to analyze the expression of IL-25 and its receptor (IL-17RB) in DICs, and the effect of IL-25 on the expression of Ki-67, IL-4, IL-10, interferon (IFN)-γ and transforming growth factor (TGF)-β in decidual γδT cells...
February 2018: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29434608/a-case-of-type-2-hypersensitivity-to-rasburicase-diagnosed-with-a-natural-killer-cell-activation-assay
#12
Sébastien Viel, Rémi Pescarmona, Alexandre Belot, Audrey Nosbaum, Christine Lombard, Thierry Walzer, Frédéric Bérard
Drug hypersensitivity reactions can lead to different clinical pictures depending on the underlying immunological mechanism. Diagnosis tests are already available to assess the most frequent drugs hypersensitivity reactions, which are mediated by specific IgE or T cells. However, it remains challenging to diagnose type 2 hypersensitivity reactions (T2HR), which can lead to severe cytopenia and liver failure. Here, we describe a case of T2HR to rasburicase, an uricolytic agent used to prevent tumor lysis syndrome...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29434597/92r-monoclonal-antibody-inhibits-human-ccr9-leukemia-cells-growth-in-nsg-mice-xenografts
#13
Beatriz Somovilla-Crespo, Maria Teresa Martín Monzón, Maria Vela, Isabel Corraliza-Gorjón, Silvia Santamaria, Jose A Garcia-Sanz, Leonor Kremer
CCR9 is as an interesting target for the treatment of human CCR9+-T cell acute lymphoblastic leukemia, since its expression is limited to immature cells in the thymus, infiltrating leukocytes in the small intestine and a small fraction of mature circulating T lymphocytes. 92R, a new mouse mAb (IgG2a isotype), was raised using the A-isoform of hCCR9 as immunogen. Its initial characterization demonstrates that binds with high affinity to the CCR9 N-terminal domain, competing with the previously described 91R mAb for receptor binding...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29433450/pathogen-recognition-by-nk-cells-amplifies-the-pro-inflammatory-cytokine-production-of-monocyte-derived-dc-via-ifn-%C3%AE
#14
Tammy Oth, Thomas H P M Habets, Wilfred T V Germeraad, Marijke I Zonneveld, Gerard M J Bos, Joris Vanderlocht
BACKGROUND: Besides their prominent role in the elimination of infected or malignantly transformed cells, natural killer (NK) cells serve as modulators of adaptive immune responses. Enhancing bidirectional crosstalk between NK cells and dendritic cells (DC) is considered a promising tool to potentiate cancer vaccines. We investigated to what extent direct sensing of viral and bacterial motifs by NK cells contributes to the response of inflammatory DC against the same pathogenic stimulus...
February 13, 2018: BMC Immunology
https://www.readbyqxmd.com/read/29431745/dkk2-imparts-tumor-immunity-evasion-through-%C3%AE-catenin-independent-suppression-of-cytotoxic-immune-cell-activation
#15
Qian Xiao, Jibo Wu, Wei-Jia Wang, Shiyang Chen, Yingxia Zheng, Xiaoqing Yu, Katrina Meeth, Mahnaz Sahraei, Alfred L M Bothwell, Lieping Chen, Marcus Bosenberg, Jianfeng Chen, Veronika Sexl, Le Sun, Lin Li, Wenwen Tang, Dianqing Wu
Immunotherapy offers new options for cancer treatment, but efficacy varies across cancer types. Colorectal cancers (CRCs) are largely refractory to immune-checkpoint blockade, which suggests the presence of yet uncharacterized immune-suppressive mechanisms. Here we report that the loss of adenomatosis polyposis coli (APC) in intestinal tumor cells or of the tumor suppressor PTEN in melanoma cells upregulates the expression of Dickkopf-related protein 2 (DKK2), which, together with its receptor LRP5, provides an unconventional mechanism for tumor immune evasion...
February 12, 2018: Nature Medicine
https://www.readbyqxmd.com/read/29429633/nk-cells-stimulate-recruitment-of-cdc1-into-the-tumor-microenvironment-promoting-cancer-immune-control
#16
Jan P Böttcher, Eduardo Bonavita, Probir Chakravarty, Hanna Blees, Mar Cabeza-Cabrerizo, Stefano Sammicheli, Neil C Rogers, Erik Sahai, Santiago Zelenay, Caetano Reis E Sousa
Conventional type 1 dendritic cells (cDC1) are critical for antitumor immunity, and their abundance within tumors is associated with immune-mediated rejection and the success of immunotherapy. Here, we show that cDC1 accumulation in mouse tumors often depends on natural killer (NK) cells that produce the cDC1 chemoattractants CCL5 and XCL1. Similarly, in human cancers, intratumoral CCL5, XCL1, and XCL2 transcripts closely correlate with gene signatures of both NK cells and cDC1 and are associated with increased overall patient survival...
February 6, 2018: Cell
https://www.readbyqxmd.com/read/29428349/clarity-bpa-effects-of-chronic-bisphenol-a-exposure-on-the-immune-system-part-1-quantification-of-the-relative-number-and-proportion-of-leukocyte-populations-in-the-spleen-and-thymus
#17
Jinpeng Li, Anthony Bach, Robert B Crawford, Ashwini S Phadnis-Moghe, Weimin Chen, Shawna D'Ingillo, Natalia Kovalova, Jose E Suarez-Martinez, Jiajun Zhou, Barbara L F Kaplan, Norbert E Kaminski
Bisphenol A (BPA) is extensively used in manufacturing of a broad range of consumer products worldwide. Due to its widespread use, human exposure to BPA is virtually ubiquitous. Broad human exposure coupled with a large scientific literature describing estrogenic activity of BPA in animals has raised public health concerns. To comprehensively evaluate the health effects of BPA exposure, a chronic toxicity study using a wide-range of BPA doses (2.5-25000 μg/kg bw/day) was conducted jointly by the NTP, thirteen NIEHS-supported grantees, and the FDA, which is called the Consortium Linking Academic and Regulatory Insights on Toxicity of BPA (CLARITY-BPA)...
February 8, 2018: Toxicology
https://www.readbyqxmd.com/read/29427786/clarity-bpa-effects-of-chronic-bisphenol-a-exposure-on-the-immune-system-part-2-characterization-of-lymphoproliferative-and-immune-effector-responses-by-splenic-leukocytes
#18
Jinpeng Li, Anthony Bach, Robert B Crawford, Ashwini S Phadnis-Moghe, Weimin Chen, Shawna D'Ingillo, Natalia Kovalova, Jose E Suarez-Martinez, Jiajun Zhou, Barbara L F Kaplan, Norbert E Kaminski
Bisphenol A (BPA) is commonly used in the manufacturing of a wide range of consumer products, including polycarbonate plastics, epoxy resin that lines beverage and food cans, and some dental sealants. Consumption of food and beverages containing BPA represents the primary route of human BPA exposure, which is virtually ubiquitous. An increasing number of studies have evaluated the effects of BPA on immune responses in laboratory animals that have reported a variety of effects some of which have been contradictory...
February 7, 2018: Toxicology
https://www.readbyqxmd.com/read/29427740/nk-18-a-promising-antimicrobial-peptide-anti-multidrug-resistant-leukemia-cells-and-lps-neutralizing-properties
#19
Jiexi Yan, Xiaolei Liang, Caijuan Bai, Lanxia Zhou, Juan Li, Kairong Wang, Yan Tang, Li Zhao
With the increase of multidrug resistance, novel anti-leukemia agents with diverse mechanisms of action are required to address this challenge. NK-18, the core region of mammalian derived protein NK-lysin, effectively inhibited the viability of both multidrug resistant and sensitive leukemia cell lines. Meanwhile, this proliferation inhibition effect was not distinct between sensitive and multidrug resistant leukemia cell line. NK-18 showed selectivity between non-tumorigenic and tumorigenic cells. It preferentially bound to tumor cells whose outer leaflet with high phosphatidylserine content...
February 7, 2018: Biochimie
https://www.readbyqxmd.com/read/29427418/high-mutation-frequency-of-the-piga-gene-in-t-cells-results-in-reconstitution-of-gpi-anchor-cd52-t-cells-that-can-give-early-immune-protection-after-alemtuzumab-based-t-cell-depleted-allogeneic-stem-cell-transplantation
#20
Floris C Loeff, J H Frederik Falkenburg, Lois Hageman, Wesley Huisman, Sabrina A J Veld, H M Esther van Egmond, Marian van de Meent, Peter A von dem Borne, Hendrik Veelken, Constantijn J M Halkes, Inge Jedema
Alemtuzumab (ALM) is used for T cell depletion in the context of allogeneic hematopoietic stem cell transplantation (alloSCT) to prevent acute graft-versus-host disease and graft rejection. Following ALM-based T cell-depleted alloSCT, relatively rapid recovery of circulating T cells has been described, including T cells that lack membrane expression of the GPI-anchored ALM target Ag CD52. We show, in a cohort of 89 human recipients of an ALM-based T cell-depleted alloSCT graft, that early lymphocyte reconstitution always coincided with the presence of large populations of T cells lacking CD52 membrane expression...
February 2, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
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