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Killer T cells cancer

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https://www.readbyqxmd.com/read/28088061/galectins-emerging-regulatory-checkpoints-linking-tumor-immunity-and-angiogenesis
#1
REVIEW
Santiago P Méndez-Huergo, Ada G Blidner, Gabriel A Rabinovich
Immune checkpoints, a plethora of inhibitory pathways aimed at maintaining immune cell homeostasis, may be co-opted by cancer cells to evade immune destruction. Therapies targeting immune checkpoints have reached a momentum yielding significant clinical benefits in patients with various malignancies by unleashing anti-tumor immunity. Galectins, a family of glycan-binding proteins, have emerged as novel regulatory checkpoints that promote immune evasive programs by inducing T-cell exhaustion, limiting T-cell survival, favoring expansion of regulatory T cells, de-activating natural killer cells and polarizing myeloid cells toward an immunosuppressive phenotype...
January 11, 2017: Current Opinion in Immunology
https://www.readbyqxmd.com/read/28075524/topk-t-lak-cell-originated-protein-kinase-inhibitor-exhibits-growth-suppressive-effect-on-small-cell-lung-cancer
#2
Jae-Hyun Park, Hiroyuki Inoue, Taigo Kato, Makda Zewde, Takashi Miyamoto, Yo Matsuo, Ravi Salgia, Yusuke Nakamura
T-lymphokine-activated killer cell-originated protein kinase (TOPK) plays critical roles in cancer cell proliferation as well as maintenance of cancer stem cells (CSC). Small cell lung cancer (SCLC) has highly aggressive phenotype, reveals early spread to distant sites, and results in dismal prognosis with little effective treatment. In this study, we demonstrate that TOPK expression was highly upregulated in both SCLC cell lines and primary tumors. Similar to siRNA-mediated TOPK knockdown effects, treatment with a potent TOPK inhibitor, OTS514, effectively suppressed growth of SCLC cell lines (IC50 ; 0...
January 11, 2017: Cancer Science
https://www.readbyqxmd.com/read/28052056/genome-wide-in-vivo-screen-identifies-novel-host-regulators-of-metastatic-colonization
#3
Louise van der Weyden, Mark J Arends, Andrew D Campbell, Tobias Bald, Hannah Wardle-Jones, Nicola Griggs, Martin Del Castillo Velasco-Herrera, Thomas Tüting, Owen J Sansom, Natasha A Karp, Simon Clare, Diane Gleeson, Edward Ryder, Antonella Galli, Elizabeth Tuck, Emma L Cambridge, Thierry Voet, Iain C Macaulay, Kim Wong, Sanger Mouse Genetics Project, Sarah Spiegel, Anneliese O Speak, David J Adams
Metastasis is the leading cause of death for cancer patients. This multi-stage process requires tumour cells to survive in the circulation, extravasate at distant sites, then proliferate; it involves contributions from both the tumour cell and tumour microenvironment ('host', which includes stromal cells and the immune system). Studies suggest the early steps of the metastatic process are relatively efficient, with the post-extravasation regulation of tumour growth ('colonization') being critical in determining metastatic outcome...
January 4, 2017: Nature
https://www.readbyqxmd.com/read/28035916/the-paired-receptors-tigit-and-dnam-1-as-targets-for-therapeutic-antibodies
#4
Natan Stein, Pinchas Tsukerman, Ofer Mandelboim
One of the most exciting fields in modern medicine is immunotherapy, treatment which looks to harness the power of the immune system to fight disease. A particularly effective strategy uses antibodies designed to influence the activity levels of the immune system. Here we look at two receptors - TIGIT and DNAM-1 - which bind the same ligands but have opposite effects on immune cells, earning them the label `paired receptors'. Importantly, natural killer cells and cytotoxic T cells express both of these receptors, and in certain cases their effector functions are dictated by TIGIT or DNAM-1 signaling...
December 23, 2016: Human Antibodies
https://www.readbyqxmd.com/read/28018354/impact-of-the-mica-129met-val-dimorphism-on-nkg2d-mediated-biological-functions-and-disease-risks
#5
REVIEW
Antje Isernhagen, Dörthe Malzahn, Heike Bickeböller, Ralf Dressel
The major histocompatibility complex (MHC) class I chain-related A (MICA) is the most polymorphic non-classical MHC class I gene in humans. It encodes a ligand for NKG2D (NK group 2, member D), an activating natural killer (NK) receptor that is expressed mainly on NK cells and CD8(+) T cells. The single-nucleotide polymorphism (SNP) rs1051792 causing a valine (Val) to methionine (Met) exchange at position 129 of the MICA protein is of specific interest. It separates MICA into isoforms that bind NKG2D with high (Met) and low affinities (Val)...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/28011506/distant-bystander-effect-of-reic-dkk3-gene-therapy-through-immune-system-stimulation-in-thoracic-malignancies
#6
Ken Suzawa, Kazuhiko Shien, Huang Peng, Masakiyo Sakaguchi, Masami Watanabe, Shinsuke Hashida, Yuho Maki, Hiromasa Yamamoto, Shuta Tomida, Junichi Soh, Hiroaki Asano, Kazunori Tsukuda, Yasutomo Nasu, Hiromi Kumon, Shinichiro Miyoshi, Shinichi Toyooka
BACKGROUND: Reduced expression in immortalized cell (REIC)/Dickkoph-3 (DKK3) is a tumor-suppressor gene, and its overexpression by adenovirus vector (Ad-REIC) exhibits a remarkable therapeutic effect on various human cancer types through a mechanism triggered by endoplasmic reticulum stress. MATERIALS AND METHODS: We examined the direct anti-tumor effect of Ad-REIC gene therapy on lung cancer and malignant mesothelioma cell lines in vitro, and the distant bystander effect using immunocompetent mouse allograft models with bilateral flank tumors...
January 2017: Anticancer Research
https://www.readbyqxmd.com/read/28005229/engaging-natural-killer-t-cells-as-universal-helpers-for-vaccination
#7
Mary Speir, Ian F Hermans, Robert Weinkove
Conventional vaccine adjuvants enhance peptide-specific T-cell and B-cell responses by modifying peptide stability or uptake or by binding to pattern-recognition receptors on antigen-presenting cells (APCs). This article discusses the application of a distinct mechanism of adjuvant activity: the activation of type I, or invariant, natural killer T (iNKT) cells to drive cellular and humoral immune responses. Using a semi-invariant T-cell receptor (TCR), iNKT cells recognize glycolipid antigens presented on cluster of differentiation (CD)-1d molecules...
December 22, 2016: Drugs
https://www.readbyqxmd.com/read/27994644/predictors-of-survival-of-natural-killer-t-cell-lymphoma-nasal-type-in-a-non-asian-population-a-single-cancer-centre-experience
#8
Jule Vásquez, Mariana Serrano, Lourdes Lopez, Cristian Pacheco, Shirley Quintana
BACKGROUND: Natural killer/T-cell lymphoma (NKTCL), part of T-cell and NK-cell neoplasms in the World Health Organisation (WHO) classification, is an aggressive lymphoma with poor prognosis more predominantly seen in Asian and South American countries. This study evaluates the factors associated with survival among patients with newly diagnosed NKTCL in Peru. METHODS: Information was abstracted from medical records (MR) for all NKTCL patients >13 years of age at the Instituto Nacional de Enfermedades Neoplasicas (INEN) between 2002 and 2011...
2016: Ecancermedicalscience
https://www.readbyqxmd.com/read/27994592/kir-genes-and-their-ligands-predict-the-response-to-anti-egfr-monoclonal-antibodies-in-solid-tumors
#9
Cristina Morales-Estevez, Juan De la Haba-Rodriguez, Barbara Manzanares-Martin, Ignacio Porras-Quintela, Antonio Rodriguez-Ariza, Alberto Moreno-Vega, Maria J Ortiz-Morales, Maria A Gomez-España, Maria T Cano-Osuna, Javier Lopez-Gonzalez, Beatriz Chia-Delgado, Rafael Gonzalez-Fernandez, Enrique Aranda-Aguilar
Killer-cell immunoglobulin-like receptors (KIRs) regulate the killing function of natural killer cells, which play an important role in the antibody-dependent cell-mediated cytotoxicity response exerted by therapeutic monoclonal antibodies (mAbs). However, it is unknown whether the extensive genetic variability of KIR genes and/or their human leukocyte antigen (HLA) ligands might influence the response to these treatments. This study aimed to explore whether the variability in KIR/HLA genes may be associated with the variable response observed to mAbs based anti-epidermal growth factor receptor (EGFR) therapies...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/27992400/the-histone-demethylase-utx-regulates-the-lineage-specific-epigenetic-program-of-invariant-natural-killer-t-cells
#10
Semir Beyaz, Ji Hyung Kim, Luca Pinello, Michael E Xifaras, Yu Hu, Jialiang Huang, Marc A Kerenyi, Partha P Das, R Anthony Barnitz, Aurelie Herault, Rizkullah Dogum, W Nicholas Haining, Ömer H Yilmaz, Emmanuelle Passegue, Guo-Cheng Yuan, Stuart H Orkin, Florian Winau
Invariant natural killer T cells (iNKT cells) are innate-like lymphocytes that protect against infection, autoimmune disease and cancer. However, little is known about the epigenetic regulation of iNKT cell development. Here we found that the H3K27me3 histone demethylase UTX was an essential cell-intrinsic factor that controlled an iNKT-cell lineage-specific gene-expression program and epigenetic landscape in a demethylase-activity-dependent manner. UTX-deficient iNKT cells exhibited impaired expression of iNKT cell signature genes due to a decrease in activation-associated H3K4me3 marks and an increase in repressive H3K27me3 marks within the promoters occupied by UTX...
February 2017: Nature Immunology
https://www.readbyqxmd.com/read/27941285/basics-of-cancer-immunotherapy
#11
Yuki Fujioka, Hiroyoshi Nishikawa
The immune system is the body's defense against infectious organisms and other invaders including cancer cells. Cancer immunotherapy, which employs our own immune systems to attack cancer cells, is now emerging as a promising modality of cancer treatment based upon the clinical successes of immune checkpoint blockade and adoptive T cell transfer. In hematologic malignancies, clinical application of anti-PD-1 mAb and CAR (chimeric antigen receptor) T therapy is now being extensively tested in Hodgkin's disease, multiple myeloma, and CD19(+) acute lymphocytic leukemia...
2016: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
https://www.readbyqxmd.com/read/27940255/arsenic-trioxide-is-an-immune-adjuvant-in-liver-cancer-treatment
#12
Lei Wang, Ren Wang, Lin Fan, Wentao Liang, Kai Liang, Yingxin Xu, Guizhu Peng, Qifa Ye
Tumor cells are inhibited effectively by As2O3in vitro and in vivo, although the underlying immune regulatory mechanisms remain unknown. Regulatory T cells play a key role in tumor immune escape. In the present study, we aimed to assess the in vivo effects of As2O3 on the immune status in hepatic cancer and its in vitro regulatory role in cytokine-induced killers(CIKs)cytotoxicity. In a tumor H22 xenograft model of hepatic cancer, we demonstrated that As2O3 treatment decreased tumor volumes and weights, and improved survival by reducing Tregs infiltration into the tumor...
January 2017: Molecular Immunology
https://www.readbyqxmd.com/read/27930550/role-of-immune-cells-in-pancreatic-cancer-from-bench-to-clinical-application-an-updated-review
#13
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/27930529/effects-of-propofol-and-sevoflurane-on-perioperative-immune-response-in-patients-undergoing-laparoscopic-radical-hysterectomy-for-cervical-cancer
#14
Songtao Liu, Xinyu Gu, Lijiao Zhu, Guannan Wu, Hai Zhou, Yan Song, Congyou Wu
The aim of this study is to compare the effects of propofol and sevoflurane anesthesia on perioperative immune response in patients undergoing laparoscopic radical hysterectomy for cervical cancer.Sixty patients with cervical cancer scheduled for elective laparoscopic radical hysterectomy under general anesthesia were randomized into 2 groups. TIVA group received propofol induction and maintenance and SEVO group received sevoflurane induction and maintenance. Blood samples were collected at 30 min before induction (T0); the end of the operation (T1); and 24 h (T2), 48 h (T3), and 72 h (T4) after operation...
December 2016: Medicine (Baltimore)
https://www.readbyqxmd.com/read/27917371/hijacker-of-the-antitumor-immune-response-autophagy-is-showing-its-worst-facet
#15
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/27899981/the-effect-and-clinical-efficacy-of-lienal-polypeptide-injection-combined-with-folfox-chemotherapy-regimen-in-colon-cancer-patients
#16
Juan Zhou, Guoping Niu, Yunfeng Pei, Chunping Cao, Chen Ding, Guangming Sun, Jing Guo, Yong Liu, Yang Yu
The aim was to investigate the clinical efficacy and immunomodulatory effect of lienal polypeptide injection combined with postoperative FOLFOX chemotherapy regimen in colon cancer patients. A total of 84 colon cancer patients were selected between January, 2014 and December, 2015. The selected patients were randomly divided into the observation (42 patients) and control (42 patients) groups. The observation group patients were treated with FOLFOX chemotherapy regimen combined with lienal polypeptide, whereas, the control group patients were treated with FOLFOX chemotherapeutic regimen only...
November 2016: Oncology Letters
https://www.readbyqxmd.com/read/27899095/effects-of-the-ayurved-siriraj-wattana-recipe-on-functional-and-phenotypic-characterization-of-cytokine-induced-killer-cells-and-dendritic-cells-in-vitro
#17
Adisak Wongkajornsilp, Nuntarak Numchaisermsuk, Khanit Sa-Ngiamsuntorn, Pravit Akarasereenont, Valla Wamanuttajinda, Kanda Kasetsinsombat, Sunisa Duangsa-Ard, Tawee Laohapan, Kittipong Maneechotesuwan
BACKGROUND: Ayurved Siriraj Wattana recipe (AVS073), has been prescribed as tonic, to increase appetite, and for pain relief. It also exhibits antioxidant, anti-inflammatory, immunomodulating and anti-cancer activities. However, the immunomodulatory effects on antigen-presenting cells and effector T cells remained elusive. We thus aimed to study the effects of AVS073 on differentiation, maturation, functions and proportions of CIK cells and monocyte-derived DCs. METHODS: CIK cells and monocyte-derived DCs were treated with AVS073, followed by the assessment of T-helper (Th) phenotypes using real-time RT-PCR and flow cytometry...
November 29, 2016: BMC Complementary and Alternative Medicine
https://www.readbyqxmd.com/read/27895918/classical-and-non-classical-hla-class-i-aberrations-in-primary-cervical-squamous-and-adenocarcinomas-and-paired-lymph-node-metastases
#18
Debbie M Ferns, A Marijne Heeren, Sanne Samuels, Maaike C G Bleeker, Tanja D de Gruijl, Gemma G Kenter, Ekaterina S Jordanova
BACKGROUND: Tumors avoid destruction by cytotoxic T cells (CTL) and natural killer (NK) cells by downregulation of classical human leukocyte antigens (HLA) and overexpression of non-classical HLA. This is the first study to investigate HLA expression in relation to histology (squamous cell carcinoma (SCC) vs. adenocarcinoma (AC)), clinicopathological parameters and survival in a large cervical cancer patient cohort. METHODS: Classical (HLA-A and HLA-B/C)- and non-classical HLA molecules (HLA-E and HLA-G) were studied on primary tumors and paired lymph node (LN) metastases from cervical cancer patients (n = 136) by immunohistochemistry...
2016: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/27895646/manufacturing-natural-killer-cells-as-medicinal-products
#19
REVIEW
Christian Chabannon, Bechara Mfarrej, Sophie Guia, Sophie Ugolini, Raynier Devillier, Didier Blaise, Eric Vivier, Boris Calmels
Natural Killer (NK) cells are innate lymphoid cells (ILC) with cytotoxic and regulatory properties. Their functions are tightly regulated by an array of inhibitory and activating receptors, and their mechanisms of activation strongly differ from antigen recognition in the context of human leukocyte antigen presentation as needed for T-cell activation. NK cells thus offer unique opportunities for new and improved therapeutic manipulation, either in vivo or in vitro, in a variety of human diseases, including cancers...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/27891129/immunological-and-translational-aspects-of-nk-cell-based-antitumor-immunotherapies
#20
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
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