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Natural killer cell immunotherapy

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https://www.readbyqxmd.com/read/28321812/optimizing-radiotherapy-with-immunotherapeutic-approaches
#1
Jonathan E Schoenhals, Tijana Skrepnik, Ugur Selek, Maria A Cortez, Ailin Li, James W Welsh
Several factors must be considered to successfully integrate immunotherapy with radiation into clinical practice. One such factor is that concepts arising from preclinical work must be tested in combination with radiation in preclinical models to better understand how combination therapy will work in patients; examples include checkpoint inhibitors, tumor growth factor-beta (TGF-β) inhibitors, and natural killer (NK) cell therapy. Also, many radiation fields and fractionation schedules typically used in radiation therapy had been standardized before the introduction of advanced techniques for radiation planning and delivery that account for changes in tumor size, location, and motion during treatment, as well as uncertainties introduced by variations in patient setup between treatment fractions...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28318556/natural-killer-cells-in-placentation-and-cancer-implications-for-hypertension-during-pregnancy
#2
Heather Yvonne Small, Denise C Cornelius, Tomasz J Guzik, Christian Delles
Hypertension during pregnancy is the most common medical condition encountered during gestation. Despite this, knowledge of the mechanisms that underlie the disease and the development of new therapies are limited. Hypertension during pregnancy and some forms of cancer confer an increased risk to the development of cardiovascular disease later in life; one mechanism which may link these conditions is the involvement of natural killer (NK) cells. Whilst immunology and immunotherapy are well-developed areas in oncology; the complex mechanisms of the immune system in health and disease at the maternal-fetal interface are less well-defined...
March 7, 2017: Placenta
https://www.readbyqxmd.com/read/28302184/cytokine-free-directed-differentiation-of-human-pluripotent-stem-cells-efficiently-produces-hemogenic-endothelium-with-lymphoid-potential
#3
Yekaterina Galat, Svetlana Dambaeva, Irina Elcheva, Aaruni Khanolkar, Kenneth Beaman, Philip M Iannaccone, Vasiliy Galat
BACKGROUND: The robust generation of human hematopoietic progenitor cells from induced or embryonic pluripotent stem cells would be beneficial for multiple areas of research, including mechanistic studies of hematopoiesis, the development of cellular therapies for autoimmune diseases, induced transplant tolerance, anticancer immunotherapies, disease modeling, and drug/toxicity screening. Over the past years, significant progress has been made in identifying effective protocols for hematopoietic differentiation from pluripotent stem cells and understanding stages of mesodermal, endothelial, and hematopoietic specification...
March 17, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28301281/cell-based-immunotherapy-with-cytokine-induced-killer-cik-cells-from-preparation-and-testing-to-clinical-application
#4
Yiming Meng, Zhifu Yu, Yefeng Wu, Tianzhao Du, Shi Chen, Fanjuan Meng, Nan Su, Yushu Ma, Xiaoxi Li, Sulan Sun, Guirong Zhang
Cell-based immunotherapy holds promise in the quest for the treatment of cancer, having potential synergy with surgery, chemotherapy and radiotherapy. As a novel approach for adoptive cell-based immunotherapy, cytokine-induced killer (CIK) cells have moved from the 'bench to bedside'. CIK cells are a heterogeneous subset of ex-vitro expanded, polyclonal T-effector cells with both natural killer (NK) and T-cell properties, which present potent non-major histocompatibility complex-restricted cytotoxicity against a variety of tumor target cells...
February 22, 2017: Human Vaccines & Immunotherapeutics
https://www.readbyqxmd.com/read/28296542/the-autophagy-machinery-restrains-inkt-cell-activation-through-cd1d1-internalization
#5
Christian W Keller, Monica Loi, Svenja Ewert, Isaak Quast, Romina Theiler, Monique Gannagé, Christian Münz, Gennaro De Libero, Stefan Freigang, Jan D Lünemann
Invariant natural killer T (iNKT) cells are innate T cells with powerful immune regulatory functions that recognize glycolipid antigens presented by the CD1D protein. While iNKT-cell-activating glycolipids are currently being explored for their efficacy to improve immunotherapy against infectious diseases and cancer, little is known about the mechanisms that control CD1D antigen presentation and iNKT cell activation in vivo. CD1D molecules survey endocytic pathways to bind lipid antigens in MHC class II containing compartments (MIICs) before recycling to the plasma membrane...
March 15, 2017: Autophagy
https://www.readbyqxmd.com/read/28295265/card9-controls-dectin-1-induced-t-cell-cytotoxicity-and-tumor-growth-in-mice
#6
Haas Tobias, Heidegger Simon, Wintges Alexander, Bscheider Michael, Bek Sarah, Fischer Julius C, Eisenkolb Gabriel, Schmickl Martina, Spoerl Silvia, Peschel Christian, Poeck Hendrik, Ruland Jürgen
Activation of the C-type lectin receptor Dectin-1 by β-glucans triggers multiple signals within dendritic cells (DCs) that result in activation of innate immunity. While these mechanisms can potently prime CD8(+) cytotoxic T cell (CTL) responses without additional adjuvants, the Dectin-1 effector pathways that control CTL induction remain unclear. Here we demonstrate that Dectin-1-induced CTL cross-priming in mice does not require inflammasome activation but strictly depends on the adapter protein Card9 in vitro...
March 10, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28294313/suppression-of-murine-tumor-growth-through-cd8-ctls-via-activated-dec-205-dendritic-cells-by-sequential-administration-of-%C3%AE-galactosylceramide-in-vivo
#7
Hideki Kogo, Masumi Shimizu, Yasuyuki Negishi, Eiji Uchida, Hidemi Takahashi
Cancer immunity is mediated through the effective priming and activation of tumor-specific class I major histocompatibility complex (MHC-I) molecule-restricted CD8(+) cytotoxic T lymphocytes (CTLs). DEC-205(+) dendritic cells (DCs) can cross-present the epitope(s) of captured tumor antigens associated with class I MHC molecules alongside co-stimulatory molecules to prime and activate tumor-specific CD8(+) CTLs. Immunosuppressive tolerogenic DCs with reduced co-stimulatory molecules may be a cause of impaired CTL induction...
March 12, 2017: Immunology
https://www.readbyqxmd.com/read/28287634/immune-microenvironment-of-gliomas
#8
Anna Gieryng, Dominika Pszczolkowska, Kacper A Walentynowicz, Wenson D Rajan, Bozena Kaminska
High-grade gliomas are rapidly progressing tumors of the central nervous system (CNS) with a very poor prognosis despite extensive resection combined with radiation and/or chemotherapy. Histopathological and flow cytometry analyses of human and rodent experimental gliomas revealed heterogeneity of a tumor and its niche, composed of reactive astrocytes, endothelial cells, and numerous immune cells. Infiltrating immune cells consist of CNS resident (microglia) and peripheral macrophages, granulocytes, myeloid-derived suppressor cells (MDSCs), and T lymphocytes...
March 13, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/28286532/efficacy-of-juzentaihoto-for-tumor-immunotherapy-in-b16-melanoma-metastasis-model
#9
Shintaro Ishikawa, Takako Ishikawa, Chiaki Tezuka, Kazuhito Asano, Masataka Sunagawa, Tadashi Hisamitsu
Introduction. Medical care for Japanese cancer patients includes Western and Kampo medicines, and treatments with juzentaihoto (JTT) reportedly prevent cancer metastasis and recurrence. In this study, we examined the effects of JTT on natural killer (NK) cell activity and metastasis in combined treatments with anti-PD-1 antibody in a mouse model of melanoma metastasis. Methods. C57BL/6 male mice were intravenously injected with B16 melanoma cells (B16 cell) and were given chow containing 3% JTT. In subsequent in vivo experiments, we assessed serum cytokine levels and tumor colony formation in the lungs...
2017: Evidence-based Complementary and Alternative Medicine: ECAM
https://www.readbyqxmd.com/read/28281564/standardized-and-flexible-eight-colour-flow-cytometry-panels-harmonized-between-different-laboratories-to-study-human-nk-cell-phenotype-and-function
#10
John P Veluchamy, María Delso-Vallejo, Nina Kok, Fenna Bohme, Ruth Seggewiss-Bernhardt, Hans J van der Vliet, Tanja D de Gruijl, Volker Huppert, Jan Spanholtz
Advancements in multi-colour fluorescence activated cell sorting (FACS) panel warrant harmonized procedures to obtain comparable data between various laboratories. The intensifying clinical exploration of Natural Killer (NK) cell-based immunotherapy demands standardized and harmonized NK cell FACS panels and acquisition protocols. Eight colour FACS panels were designed to study human NK cell phenotype and function within peripheral blood mononuclear cells (PBMC). The panels were designed around fixed backbone markers and channels, covering antigens for non-NK lineage exclusion (CD3, TCRγδ, CD19, CD14, SYTOX(®) Blue) and NK cell selection (CD45, CD56, CD16), complemented with variable drop-in markers/channels to study NK cell phenotype (NKG2A, NKG2C, NKG2D and KIR2D) or NK cell function and activation (CD25, NKp44 and CD107a)...
March 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28280786/global-dynamics-of-a-colorectal-cancer-treatment-model-with-cancer-stem-cells
#11
Kristen Abernathy, Zachary Abernathy, Kelsey Brown, Claire Burgess, Rebecca Hoehne
We present and analyze a mathematical model of the treatment of colorectal cancer using a system of nonlinear ordinary differential equations. The model describes the effectiveness of immunotherapy and chemotherapy for treatment of tumor cells and cancer stem cells (CSCs). The effects of CD8(+)T cells, natural killer cells, and interleukin proteins on tumor cells and CSCs under the influence of treatment are also illustrated. Using the method of localization of compact invariant sets, we present conditions on treatment parameters to guarantee a globally attracting tumor clearance state...
February 2017: Heliyon
https://www.readbyqxmd.com/read/28280089/successful-transfer-of-umbilical-cord-blood-cd34-hematopoietic-stem-and-progenitor-derived-nk-cells-in-older-acute-myeloid-leukemia-patients
#12
Harry Dolstra, Mieke W H Roeven, Jan Spanholtz, Basav N Hangalapura, Marleen Tordoir, Frans Maas, Marij Leenders, Fenna Bohme, Nina Kok, Carel Trilsbeek, Jos Paardekooper, Anniek B van der Waart, Peter E Westerweel, Tjeerd J F Snijders, Jan J Cornelissen, Gerard M J Bos, Hans F M Pruijt, Aniek O De Graaf, Bert van der Reijden, Joop H Jansen, Arnold van der Meer, Gerwin Huls, Jeannette Cany, Frank Preijers, Nicole M A Blijlevens, Nicolaas M Schaap
PURPOSE: Older acute myeloid leukemia (AML) patients have a poor prognosis, therefore novel therapies are needed. Allogeneic natural killer (NK) cells have been adoptively transferred with promising clinical results. Here, we report the first-in-human study exploiting an unique scalable NK cell product generated ex vivo from CD34+ hematopoietic stem and progenitor cells (HSPCs) from partially HLA-matched umbilical cord blood units. EXPERIMENTAL DESIGN: Ten older AML patients in morphologic complete remission received an escalating HSPC-NK cell dose (between 3 and 30x10^6/kg body weight) after lymphodepleting chemotherapy without cytokine boosting...
March 9, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28258695/tigit-and-cd96-new-checkpoint-receptor-targets-for-cancer-immunotherapy
#13
REVIEW
William C Dougall, Sema Kurtulus, Mark J Smyth, Ana C Anderson
While therapies targeting the co-inhibitory or immune checkpoint receptors PD-1 and CTLA-4 have shown remarkable success in many cancers, not all patients benefit from these therapies. This has catalyzed enormous interest in the targeting of other immune checkpoint receptors. In this regard, TIGIT and CD96 have recently entered the limelight as novel immune checkpoint receptor targets. TIGIT and CD96 together with the co-stimulatory receptor CD226 form a pathway that is analogous to the CD28/CTLA-4 pathway, in which shared ligands and differential receptor:ligand affinities fine-tune the immune response...
March 2017: Immunological Reviews
https://www.readbyqxmd.com/read/28236750/targeting-nk-cell-checkpoints-for-cancer-immunotherapy
#14
REVIEW
Aura Muntasell, Maria C Ochoa, Luna Cordeiro, Pedro Berraondo, Ascension López-Díaz de Cerio, Mariona Cabo, Miguel López-Botet, Ignacio Melero
Natural Killer (NK) cells are cytotoxic lymphocytes specialized in early defense against virus-infected and transformed cells. NK-cell function is regulated by activating and inhibitory surface receptors recognizing their ligands on transformed cells. Modulation of NK numbers and/or function by a variety of agents such as cytokines and monoclonal antibodies may result in enhanced anti-tumor activity. Recombinant cytokines (i.e., IL-15 and IL-2), antibodies blocking inhibitory receptors (i.e., KIR, NKG2A and TIGIT) and agonists delivering signals via CD137, NKG2D and CD16 stand out as the most suitable opportunities...
February 22, 2017: Current Opinion in Immunology
https://www.readbyqxmd.com/read/28218426/dkk3-attenuates-the-cytotoxic-effect-of-natural-killer-cells-on-cd133-gastric-cancer-cells
#15
Pu Xia, Xiao-Yan Xu
Cancer stem cell (CSCs) has started a new era in cancer research. CD133 is a widely used marker for identification of CSCs. More and more studies showed that NK cells preferentially target cancer stem-like cells. However, the deeper mechanism of the susceptibility of cancer stem cells to NK cells remains unclear. In this study, we isolated CD133 positive population of a gastric cancer cell line, BGC823 cells, and cultured with NK cells. We found that CD133 could efficiently active NK cells in an NKG2D-dependent manner...
February 20, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/28201977/targeting-the-immune-niche-within-the-bone-marrow-microenvironment-the-rise-of-immunotherapy-in-multiple-myeloma
#16
Klaus Podar, D Jäger
Multiple Myeloma (MM) cells inhibit the development of an effective anti-MM immune response via defects in T cell function, ineffective antigen presentation; reduced phagocytic capacity; natural killer and dendritic cell dysfunction; decreased responsiveness to IL-2 and defects in B cell immunity; upregulation of inhibitory pathways; and production of excessive pro-inflammatory cytokines. Moreover, immune cells including plasmacytoid dendritic cells and macrophages trigger tumor cell proliferation, survival, and drug resistance...
February 13, 2017: Current Cancer Drug Targets
https://www.readbyqxmd.com/read/28195314/reversal-of-tumor-acidosis-by-systemic-buffering-reactivates-nk-cells-to-express-ifn-%C3%AE-and-induces-nk-cell-dependent-lymphoma-control-without-other-immunotherapies
#17
Johann Pötzl, David Roser, Lorenz Bankel, Nadine Hömberg, Albert Geishauser, Christoph D Brenner, Michael Weigand, Martin Röcken, Ralph Mocikat
Like other immune cells, natural killer (NK) cells show impaired effector functions in the microenvironment of tumors, but little is known on the underlying mechanisms. Since lactate acidosis, a hallmark of malignant tissue, was shown to contribute to suppression of effective antitumor immune responses, we investigated the impact of tissue pH and lactate concentration on NK-cell functions in an aggressive model of endogenously arising B-cell lymphoma. The progressive loss of IFN-γ production by NK cells observed during development of this disease could be ascribed to decreased pH values and lactate accumulation in the microenvironment of growing tumors...
May 1, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28191816/interferon-%C3%AE-inducible-dendritic-cells-matured-with-ok-432-exhibit-trail-and-fas-ligand-pathway-mediated-killer-activity
#18
Terutsugu Koya, Ryu Yanagisawa, Yumiko Higuchi, Kenji Sano, Shigetaka Shimodaira
Active human dendritic cells (DCs), which efficiently induce immune responses through their functions as antigen-presenting cells, exhibit direct anti-tumour killing activity in response to some pathogens and cytokines. These antigen-presenting and tumour killing abilities may provide a breakthrough in cancer immunotherapy. However, the mechanisms underlying this killer DC activity have not been fully proven, despite the establishment of interferon-α (IFN-α)-generated killer DCs (IFN-DCs). Here mature IFN-DCs (mIFN-DCs), generated from IFN-DCs primed with OK-432 (streptococcal preparation), exhibited elevated expression of CD86 and human leukocyte antigen-DR (minimum criteria for DC vaccine clinical trials) as well as antigen-presenting abilities comparable with those of mature IL-4-DCs (mIL-4-DCs)...
February 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28186088/current-status-of-immunotherapy-for-gastrointestinal-stromal-tumor
#19
REVIEW
Y Tan, J C Trent, B A Wilky, D A Kerr, A E Rosenberg
Gastrointestinal stromal tumors (GIST) contain tumor-infiltrating immune cells and their presence provides an opportunity and rationale for developing effective forms of immunotherapy. The types of tumor-infiltrating inflammatory cells and relevant immune checkpoint inhibitors are the focus of active investigation. The most numerous tumor-infiltrating inflammatory cells are tumor-associated macrophages (TAMs) and CD3+ T cells. Studies have shown that patients with GISTs that harbor increased numbers of CD3+ T cells have better outcomes...
February 10, 2017: Cancer Gene Therapy
https://www.readbyqxmd.com/read/28186087/baculovirus-directly-activates-murine-nk-cells-via-tlr9
#20
T Moriyama, T Suzuki, M O Chang, M Kitajima, H Takaku
The importance of natural killer (NK) cells in innate immune responses against tumors or viral infections enhances the appeal of NK cell-based immunotherapeutic approaches. We have recently reported that baculovirus (BV)-infected dendritic cells (DCs; BV-DCs) induce antitumor immunity against established tumors in mice. These antitumor effects were CD8(+) T-cell and NK cell dependent; however, they were found to be CD4(+) T-cell independent. In this study, we investigated the involvement of Toll-like receptor 9 (TLR9) in the process of BV recognition by NK cells...
February 10, 2017: Cancer Gene Therapy
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