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Natural killer cell immunotherapy

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https://www.readbyqxmd.com/read/29147621/in-depth-immunophenotyping-of-patients-with-glioblastoma-multiforme-impact-of-steroid-treatment
#1
Guranda Chitadze, Charlotte Flüh, Elgar Susanne Quabius, Sandra Freitag-Wolf, Christian Peters, Marcus Lettau, Jaydeep Bhat, Daniela Wesch, Hans-Heinrich Oberg, Stefanie Luecke, Ottmar Janssen, Michael Synowitz, Janka Held-Feindt, Dieter Kabelitz
Despite aggressive treatment regimens based on surgery and radiochemotherapy, the prognosis of patients with grade IV glioblastoma multiforme (GBM) remains extremely poor, calling for alternative options such as immunotherapy. Immunological mechanisms including the Natural Killer Group 2 member D (NKG2D) receptor-ligand system play an important role in tumor immune surveillance and targeting the NKG2D system might be beneficial. However, before considering any kind of immunotherapy, a precise characterization of the immune system is important, particularly in GBM patients where conventional therapies with impact on the immune system are frequently co-administered...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/29137237/cryoablation-combined-with-allogenic-natural-killer-cell-immunotherapy-improves-the-curative-effect-in-patients-with-advanced-hepatocellular-cancer
#2
Mao Lin, Shuzhen Liang, Xiaohua Wang, Yinqing Liang, Mingjie Zhang, Jibing Chen, Lizhi Niu, Kecheng Xu
In this study, the clinical efficacy of cryosurgery combined with allogenic natural killer cell immunotherapy for advanced hepatocellular cancer was evaluated. From October 2015 to March 2017, we enrolled 61 patients who met the enrollment criteria and divided them into two groups: 1) the simple cryoablation group (Cryo group, n = 26); and 2) the cryoablation combined with allogenic natural killer cells group (Cryo-NK group, n = 35), the safety and short-term effects were evaluated firstly, then the median progression-free survival, response rate and disease control rate were assessed...
October 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29133133/boosting-natural-killer-cell-based-immunotherapy-with-anticancer-drugs-a-perspective
#3
REVIEW
Loredana Cifaldi, Franco Locatelli, Emiliano Marasco, Lorenzo Moretta, Vito Pistoia
Natural killer (NK) cells efficiently recognize and kill tumor cells through several mechanisms including the expression of ligands for NK cell-activating receptors on target cells. Different clinical trials indicate that NK cell-based immunotherapy represents a promising antitumor treatment. However, tumors develop immune-evasion strategies, including downregulation of ligands for NK cell-activating receptors, that can negatively affect antitumor activity of NK cells, which either reside endogenously, or are adoptively transferred...
November 10, 2017: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/29130994/enhancement-of-anti-leukemia-immunity-by-leukemia-derived-exosomes-via-downregulation-of-tgf-%C3%AE-1-expression
#4
Fang Huang, Jiangbo Wan, Weiwei Hu, Siguo Hao
BACKGROUND/AIMS: Minimal residual leukemia cells (MRLs) are difficult to eradicate through traditional treatment and therefore remain to be a major threat to the long-term survival of leukemia patients. Tumor-derived exosomes (TEXs), which carry tumor associated antigens (TAA), may be a potential cell-free tumor vaccine for the specific eradication of MRLs. However, TEXs are intended to be less immunogenic due to exosomal TGF-β1. To further optimize the efficacy of TEX-based vaccines, we investigated whether exosomes from TGF-β1 silenced leukemia cells (LEXTGF-β1si) had an increased potential to induce a specific antitumor effect compared with non-modified exosomes...
November 9, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29123966/pd-1-blockade-at-the-time-of-tumor-escape-potentiates-the-immune-mediated-antitumor-effects-of-a-melanoma-targeting-monoclonal-antibody
#5
Laetitia They, Henri-Alexandre Michaud, Ondine Becquart, Virginie Lafont, Bernard Guillot, Florence Boissière-Michot, Marta Jarlier, Caroline Mollevi, Jean-François Eliaou, Nathalie Bonnefoy, Laurent Gros
Tumor antigen-targeting monoclonal antibodies (TA-targeting mAbs) are used as therapeutics in many malignancies and their capacity to mobilize the host immunity puts them at the forefront of anti-cancer immunotherapies. Both innate and adaptive immune cells have been associated with the therapeutic activity of such antibodies, but tumor escape from mAb-induced tumor immune surveillance remains one of the main clinical issues. In this preclinical study, we grafted immunocompetent and immunocompromised mice with the B16F10 mouse melanoma cell line and treated them with the TA99 TA-targeting mAb to analyze the immune mechanisms associated with the tumor response and resistance to TA99 monotherapy...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/29122934/genotyping-natural-killer-immune-checkpoints%C3%A2-to-discover-biomarkers-of-response
#6
Nai-Kong V Cheung, Katharine C Hsu
Immune checkpoints have been a focus of immunotherapy in the recent decade. Killer-cell immunoglobulin-like receptors (KIR) and their cognate human leukocyte antigen (HLA) class I ligands have evolved as checkpoints to ensure self-tolerance of natural iiller (NK) cells. Both KIR and HLA genetic profiles are potential biomarkers of immunotherapy outcome.
November 9, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29118009/immunotherapy-targeting-4-1bb-mechanistic-rationale-clinical-results-and-future-strategies
#7
Cariad Chester, Miguel F Sanmamed, Jun Wang, Ignacio Melero
4-1BB (CD137, TNFRSF9) is an inducible costimulatory receptor expressed on activated T and natural killer (NK) cells. 4-1BB ligation on T cells triggers a signaling cascade that results in upregulation of antiapoptotic molecules, cytokine secretion, and enhanced effector function. In dysfunctional T cells that have a decreased cytotoxic capacity, 4-1BB ligation demonstrates a potent ability to restore effector functions. On NK cells, 4-1BB signaling can increase antibody-dependent cell-mediated cytotoxicity...
November 8, 2017: Blood
https://www.readbyqxmd.com/read/29113227/low-dose-valproic-acid-with-low-dose-gemcitabine-augments-mhc-class-i-related-chain-a-b-expression-without-inducing-the-release-of-soluble-mhc-class-i-related-chain-a-b
#8
Tomoharu Miyashita, Kenji Miki, Takashi Kamigaki, Isamu Makino, Hidehiro Tajima, Shinichi Nakanuma, Hironori Hayashi, Hiroyuki Takamura, Sachio Fushida, Ali K Ahmed, John W Harmon, Tetsuo Ohta
To improve natural killer group 2 member D (NKG2D)-dependent cytotoxicity, the inhibition of cleavage and release of major histocompatibility complex class 1-related chain (MIC) molecules from the tumor surface are required. Valproic acid (VPA), a histone deacetylase (HDAC) inhibitor, is able to induce cell-surface MICA/B on tumor cells. In the present study, the ability of VPA and gemcitabine (GEM) to upregulate MICA/B in pancreatic cancer cells was investigated, resulting in the inhibition of cleavage and release of MIC molecules from the tumor surface...
November 2017: Oncology Letters
https://www.readbyqxmd.com/read/29112124/gene-regulatory-network-rewiring-in-the-immune-cells-associated-with-cancer
#9
Pengyong Han, Chandrasekhar Gopalakrishnan, Haiquan Yu, Edwin Wang
The gene regulatory networks (GRNs) of immune cells not only indicate cell identity but also reveal the dynamic changes of immune cells when comparing their GRNs. Cancer immunotherapy has advanced in the past few years. Immune-checkpoint blockades (i.e., blocking PD-1, PD-L1, or CTLA-4) have shown durable clinical effects on some patients with various advanced cancers. However, major gaps in our knowledge of immunotherapy have been recognized. To fill these gaps, we conducted a systematic analysis of the GRNs of key immune cell subsets (i...
November 7, 2017: Genes
https://www.readbyqxmd.com/read/29109728/invariant-natural-killer-t-cells-in-immune-regulation-of-blood-cancers-harnessing-their-potential-in-immunotherapies
#10
REVIEW
Pui Yeng Lam, Michael D Nissen, Stephen R Mattarollo
Invariant natural killer T (iNKT) cells are a unique innate T lymphocyte population that possess cytolytic properties and profound immunoregulatory activities. iNKT cells play an important role in the immune surveillance of blood cancers. They predominantly recognize glycolipid antigens presented on CD1d, but their activation and cytolytic activities are not confined to CD1d expressing cells. iNKT cell stimulation and subsequent production of immunomodulatory cytokines serve to enhance the overall antitumor immune response...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29103317/anticancer-cellular-immunotherapies-derived-from-umbilical-cord-blood
#11
Katalin Balassa, Vanderson Rocha
Introduction The lack of highly effective drugs in many malignancies has prompted scientific interest in the development of alternative treatment strategies. Cellular immunotherapy involving the adoptive transfer of immune cells that potently recognize and eliminate malignantly transformed cells has become a promising new tool in the anticancer armory. Studies suggest that the unique biological properties of umbilical cord blood (UCB) cells could precipitate enhanced anticancer activity; hence, UCB could be an optimal source for immunotherapy with the potential to provide products with "off-the-shelf" availability...
November 6, 2017: Expert Opinion on Biological Therapy
https://www.readbyqxmd.com/read/29097997/the-more-the-better-do-the-right-thing-for-natural-killer-immunotherapy-in-acute-myeloid-leukemia
#12
REVIEW
Sarah Parisi, Mariangela Lecciso, Darina Ocadlikova, Valentina Salvestrini, Marilena Ciciarello, Dorian Forte, Giulia Corradi, Michele Cavo, Antonio Curti
Natural killer (NK) cells are circulating CD3(-) lymphocytes, which express CD56 or CD16 and an array of inhibitory receptors, called killer-immunoglobulin-like receptors (KIRs). Alloreactive KIR-ligand mismatched NK cells crucially mediate the innate immune response and have a well-recognized antitumor activity. Adoptive immunotherapy with alloreactive NK cells determined promising clinical results in terms of response in acute myeloid leukemia (AML) patients and several data demonstrated that response can be influenced by the composition of NK graft...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29093083/dynamics-of-sendai-virus-spread-clearance-and-immunotherapeutic-efficacy-after-hematopoietic-cell-transplant-imaged-non-invasively-in-mice
#13
Heba H Mostafa, Peter Vogel, Ashok Srinivasan, Charles J Russell
There are no approved vaccines or virus-specific treatments for human parainfluenza viruses (PIVs), which have recently been reclassified into species human respirovirus 1 and 3 and human rubulavirus 2 and 4 These viruses cause morbidity and mortality in immunocompromised patients including those undergoing hematopoietic cell transplant (HCT). No small-animal models exist for non-invasive imaging of respiratory viral infection in the HCT host despite the utility such a system would offer to monitor prolonged infection, its clearance, and treatment options...
November 1, 2017: Journal of Virology
https://www.readbyqxmd.com/read/29089892/is-there-an-opportunity-for-current-chemotherapeutics-to-up-regulate-mic-a-b-ligands
#14
Kendel Quirk, Shanmugasundaram Ganapathy-Kanniappan
Natural killer (NK) cells are critical effectors of the immune system. NK cells recognize unhealthy cells by specific ligands [e.g., MHC- class I chain related protein A or B (MIC-A/B)] for further elimination by cytotoxicity. Paradoxically, cancer cells down-regulate MIC-A/B and evade NK cell's anticancer activity. Recent data indicate that cellular-stress induces MIC-A/B, leading to enhanced sensitivity of cancer cells to NK cell-mediated cytotoxicity. In this Perspective article, we hypothesize that current chemotherapeutics at sub-lethal, non-toxic dose may promote cellular-stress and up-regulate the expression of MIC-A/B ligands to augment cancer's sensitivity to NK cell-mediated cytotoxicity...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29078283/humanized-mouse-model-supports-development-function-and-tissue-residency-of-human-natural-killer-cells
#15
Dietmar Herndler-Brandstetter, Liang Shan, Yi Yao, Carmen Stecher, Valerie Plajer, Melanie Lietzenmayer, Till Strowig, Marcel R de Zoete, Noah W Palm, Jie Chen, Catherine A Blish, Davor Frleta, Cagan Gurer, Lynn E Macdonald, Andrew J Murphy, George D Yancopoulos, Ruth R Montgomery, Richard A Flavell
Immunodeficient mice reconstituted with a human immune system represent a promising tool for translational research as they may allow modeling and therapy of human diseases in vivo. However, insufficient development and function of human natural killer (NK) cells and T cell subsets limit the applicability of humanized mice for studying cancer biology and therapy. Here, we describe a human interleukin 15 (IL15) and human signal regulatory protein alpha (SIRPA) knock-in mouse on a Rag2(-/-)Il2rg(-/-) background (SRG-15)...
October 25, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29078276/targeting-autophagy-inhibits-melanoma-growth-by-enhancing-nk-cells-infiltration-in-a-ccl5-dependent-manner
#16
Takouhie Mgrditchian, Tsolere Arakelian, Jérôme Paggetti, Muhammad Zaeem Noman, Elodie Viry, Etienne Moussay, Kris Van Moer, Stephanie Kreis, Coralie Guerin, Stephanie Buart, Caroline Robert, Christophe Borg, Philippe Vielh, Salem Chouaib, Guy Berchem, Bassam Janji
While blocking tumor growth by targeting autophagy is well established, its role on the infiltration of natural killer (NK) cells into tumors remains unknown. Here, we investigate the impact of targeting autophagy gene Beclin1 (BECN1) on the infiltration of NK cells into melanomas. We show that, in addition to inhibiting tumor growth, targeting BECN1 increased the infiltration of functional NK cells into melanoma tumors. We provide evidence that driving NK cells to the tumor bed relied on the ability of autophagy-defective tumors to transcriptionally overexpress the chemokine gene CCL5 Such infiltration and tumor regression were abrogated by silencing CCL5 in BECN1-defective tumors...
October 31, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29075492/erratum-allogenic-natural-killer-cell-immunotherapy-of-sizeable-ovarian-cancer-a-case-report
#17
Silun Xie, Jibing Chen, Mingjiie Zhang, Zhengyi Wu
[This corrects the article DOI: 10.3892/mco.2017.1230.].
November 2017: Molecular and Clinical Oncology
https://www.readbyqxmd.com/read/29067879/expression-of-disialoganglioside-gd2-in-neuroblastic-tumors-a-prognostic-value-for-patients-treated-with-anti-gd2-immunotherapy
#18
Tatjana Terzic, Martine Cordeau, Sabine Herblot, Pierre Teira, Sonia Cournoyer, Mona Beaunoyer, Michel Peuchmaur, Michel Duval, Herve Sartelet
Neuroblastoma, a malignant neoplasm of the sympathetic nervous system, is one of the most aggressive pediatric cancers. Patients with stage IV high-risk neuroblastoma receive an intensive multimodal therapy ending with an immunotherapy based on a chimeric monoclonal antibody ch14.18. Although the use of ch14.18 monoclonal antibody has significantly increased the survival rate of high-risk neuroblastoma patients, about 33% of these patients still relapse and die from their disease. Ch14.18 targets the disialoganglioside, GD2, expressed on neuroblastic tumor (NT) cells...
January 1, 2017: Pediatric and Developmental Pathology
https://www.readbyqxmd.com/read/29054890/natural-killer-t-cell-immunotherapy-in-combination-with-chemotherapy-induced-immunogenic-cell-death-targets-metastatic-breast-cancer
#19
Simon Gebremeskel, Lynnea Lobert, Kaitlyn Tanner, Brynn Walker, Tora Oliphant, Livia E Clarke, Graham Dellaire, Brent Johnston
Natural killer T (NKT) cells are glycolipid-reactive lymphocytes that promote cancer control. In previous studies, NKT-cell activation improved survival and antitumor immunity in a post-surgical mouse model of metastatic breast cancer. Herein, we investigated whether NKT-cell activation could be combined with chemotherapeutic agents to augment therapeutic outcomes. Gemcitabine and cyclophosphamide analogs enhanced the potential immunogenicity of 4T1 mammary carcinoma cells by increasing the expression of antigen-presenting molecules (MHC-I, MHC-II, and CD1d) and promoting exposure or release of immunogenic cell death markers (calreticulin, HMGB1 and ATP)...
October 20, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/29042417/restoration-of-natural-killer-cell-anti-metastatic-activity-by-il-12-and-checkpoint-blockade
#20
Isabel Ohs, Laura Ducimetiere, Joana Marinho, Paulina Kulig, Burkhard Becher, Sonia Tugues
Immune checkpoint therapies target tumor antigen-specific T cells, but less is known about their effects on natural killer (NK) cells, which help control metastasis. In studying the development of lung metastases, we found that NK cells lose their cytotoxic capacity and acquire a molecular signature defined by the expression of co-inhibitory receptors. In an effort to overcome this suppressive mechanism, we evaluated NK cell responses to the immunostimulatory cytokine IL-12. Exposure to IL-12 rescued the cytotoxicity of NK cells but also led to the emergence of an immature NK cell population which expressed high levels of the co-inhibitory molecules PD-1, Lag-3 and TIGIT, thereby limiting NK cell-mediated control of pulmonary metastases...
October 17, 2017: Cancer Research
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