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https://www.readbyqxmd.com/read/28201977/targeting-the-immune-niche-within-the-bone-marrow-microenvironment-the-rise-of-immunotherapy-in-multiple-myeloma
#1
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/28191010/role-of-dietary-metabolites-in-regulating-the-host-immune-response-in-gastrointestinal-disease
#2
REVIEW
Mohamad El-Zaatari, John Y Kao
The host immune response to gastrointestinal (GI) infections, hypersensitivity reactions, or GI cancers comprises numerous pathways that elicit responses on different host cells. Some of these include (1) the stimulation of mast cells via their IgE receptor, (2) the production of antibodies leading to antibody-mediated cytotoxic T/natural killer cell killing, (3) the activation of the complement pathway, and (4) the activation of the adaptive immune response via antigen-presenting cell, T cell, and B cell interactions...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28186088/current-status-of-immunotherapy-for-gastrointestinal-stromal-tumor
#3
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
#4
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
https://www.readbyqxmd.com/read/28184223/fc-engineering-for-developing-therapeutic-bispecific-antibodies-and-novel-scaffolds
#5
REVIEW
Hongyan Liu, Abhishek Saxena, Sachdev S Sidhu, Donghui Wu
Therapeutic monoclonal antibodies have become molecules of choice to treat autoimmune disorders, inflammatory diseases, and cancer. Moreover, bispecific/multispecific antibodies that target more than one antigen or epitope on a target cell or recruit effector cells (T cell, natural killer cell, or macrophage cell) toward target cells have shown great potential to maximize the benefits of antibody therapy. In the past decade, many novel concepts to generate bispecific and multispecific antibodies have evolved successfully into a range of formats from full bispecific immunoglobulin gammas to antibody fragments...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28181907/the-role-of-interleukin-15-in-neoplasia
#6
Małgorzata Chłopek, Artur Kowalik, Stanisław Góźdź, Katarzyna Koziak
Interleukin 15 is a pleiotropic cytokine of the four α helix bundle family. Binding to a heterotrimeric receptor complex, which consists of a unique, high affinity IL‑15Rα‑chain and IL-2/IL-15Rβ and IL‑2Rγ chains, IL‑15 activates signaling pathways leading to activation and proliferation of T and B cells, as well as natural killer cells. At the same time, IL‑15 protects effector cells from T regulatory cells and does not induce immune tolerance. The significant regulatory action of IL‑15 on the immune system provides new opportunities for development of anti‑cancer therapies...
January 10, 2017: Postȩpy Higieny i Medycyny Doświadczalnej
https://www.readbyqxmd.com/read/28165478/a-distinct-innate-lymphoid-cell-population-regulates-tumor-associated-t-cells
#7
Sarah Q Crome, Linh T Nguyen, Sandra Lopez-Verges, S Y Cindy Yang, Bernard Martin, Jennifer Y Yam, Dylan J Johnson, Jessica Nie, Michael Pniak, Pei Hua Yen, Anca Milea, Ramlogan Sowamber, Sarah Rachel Katz, Marcus Q Bernardini, Blaise A Clarke, Patricia A Shaw, Philipp A Lang, Hal K Berman, Trevor J Pugh, Lewis L Lanier, Pamela S Ohashi
Antitumor T cells are subject to multiple mechanisms of negative regulation. Recent findings that innate lymphoid cells (ILCs) regulate adaptive T cell responses led us to examine the regulatory potential of ILCs in the context of cancer. We identified a unique ILC population that inhibits tumor-infiltrating lymphocytes (TILs) from high-grade serous tumors, defined their suppressive capacity in vitro, and performed a comprehensive analysis of their phenotype. Notably, the presence of this CD56(+)CD3(-) population in TIL cultures was associated with reduced T cell numbers, and further functional studies demonstrated that this population suppressed TIL expansion and altered TIL cytokine production...
February 6, 2017: Nature Medicine
https://www.readbyqxmd.com/read/28154014/a-tumor-cell-selective-inhibitor-of-mitogen-activated-protein-kinase-phosphatases-sensitizes-breast-cancer-cells-to-lymphokine-activated-killer-cell-activity
#8
Christof T Kaltenmeier, Laura L Vollmer, Lawrence A Vernetti, Lindsay Caprio, Keanu Davis, Vasiliy N Korotchenko, Billy W Day, Michael Tsang, Keren I Hulkower, Michael T Lotze, Andreas Vogt
Dual specificity mitogen activated protein kinase (MAPK) phosphatases (DUSP-MKPs) have been hypothesized to maintain cancer cell survival by buffering excessive MAPK signaling caused by upstream activating oncogenic products. A large and diverse body of literature suggests that genetic depletion of DUSP-MKPs can reduce tumorigenicity, suggesting that hyperactivating MAPK signaling by DUSP-MKP inhibitors could be a novel strategy to selectively affect the transformed phenotype. Through in vivo structure activity relationship studies in transgenic zebrafish we recently identified a hyperactivator of Fibroblast Growth Factor signaling (BCI-215) that is devoid of developmental toxicity and restores defective MAPK activity caused by overexpression of DUSP1 and DUSP6 in mammalian cells...
February 2, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28151486/star-pap-a-poly-a-polymerase-functions-as-a-tumor-suppressor-in-an-orthotopic-human-breast-cancer-model
#9
C Yu, Y Gong, H Zhou, M Wang, L Kong, J Liu, T An, H Zhu, Y Li
Star-PAP is a noncanonical poly(A) polymerase and required for the expression of a select set of mRNAs. However, the pathological role of Star-PAP in cancer largely remains unknown. In this study, we observed decreased expression of Star-PAP in breast cancer cell lines and tissues. Ectopic Star-PAP expression inhibited proliferation as well as colony-forming ability of breast cancer cells. In breast cancer patients, high levels of Star-PAP correlated with an improved prognosis. Moreover, by regulating the expression of BIK (BCL2-interacting killer), Star-PAP induced apoptosis of breast cancer cells through the mitochondrial pathway...
February 2, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28138440/inverse-correlation-between-cd8-inflammatory-cells-and-e-cadherin-expression-in-gallbladder-cancer-tissue-microarray-and-imaging-analysis
#10
Keita Kai, Masanori Masuda, Shinichi Aishima
AIM: To investigated the association between the tumor cells' expression of E-cadherin and the numbers of several types of inflammatory cells infiltrating into the invasive portion of gallbladder cancer (GBC). METHODS: We analyzed 50 GBC cases for which a sufficient amount of tumor tissues for tissue microarray (TMA) had been saved. Three tissue cores (3.0 mm) of invasive lesion from each case were used for the TMA. The 4-μm cut sections on slides were immunostained using primary antibodies including E-cadherin for cancer cells, leukocyte common antigen for leukocyte, myeloperoxidase for neutrophils, CD3 for T cells, CD4 for helper T cells, CD8 for killer T cells, CD20 for B cells and CD68 for macrophages...
January 16, 2017: World Journal of Clinical Cases
https://www.readbyqxmd.com/read/28135606/hla-g-variability-and-haplotypes-detected-by-massively-parallel-sequencing-procedures-in-the-geographicaly-distinct-population-samples-of-brazil-and-cyprus
#11
Erick C Castelli, Petroula Gerasimou, Michelle A Paz, Jaqueline Ramalho, Iane O P Porto, Thálitta H A Lima, Andréia S Souza, Luciana C Veiga-Castelli, Cristhianna V A Collares, Eduardo A Donadi, Celso T Mendes-Junior, Paul Costeas
The HLA-G molecule presents immunomodulatory properties that might inhibit immune responses when interacting with specific Natural Killer and T cell receptors, such as KIR2DL4, ILT2 and ILT4. Thus, HLA-G might influence the outcome of situations in which fine immune system modulation is required, such as autoimmune diseases, transplants, cancer and pregnancy. The majority of the studies regarding the HLA-G gene variability so far was restricted to a specific gene segment (i.e., promoter, coding or 3' untranslated region), and was performed by using Sanger sequencing and probabilistic models to infer haplotypes...
March 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28121454/igg-antibody-response-elicited-by-a-fully-synthetic-two-component-carbohydrate-based-cancer-vaccine-candidate-with-%C3%AE-galactosylceramide-as-built-in-adjuvant
#12
Xu-Guang Yin, Xiang-Zhao Chen, Wen-Mei Sun, Xiao-Shan Geng, Xiao-Kang Zhang, Jian Wang, Pan-Pan Ji, Zhong-Yin Zhou, Dong Jae Baek, Guang-Fu Yang, Zheng Liu, Jun Guo
A fully synthetic self-adjuvanting cancer vaccine candidate was constructed through covalent conjugation of invariant natural killer T (iNKT) cell ligand α-galactosylceramide (αGalCer) with sialyl Tn (STn), a representative tumor-associated carbohydrate antigen (TACA). This two-component vaccine STn-αGalCer is devoid of antigenic peptide, featuring the well-defined structure with high simplicity. STn-αGalCer showed remarkable efficacy in inducing antibody class switching from IgM to STn-specific IgG. Subtypes of IgG antibody were primarily IgG1 and IgG3...
January 25, 2017: Organic Letters
https://www.readbyqxmd.com/read/28121242/can-killers-be-saviors
#13
G Singh, A K Agarwal, J Prosek, M S K Jayadev, A Singh
Autoimmunity and cancer have a multifarious epidemiology. Often, it is because of an impaired genome, culminating in functional aberrations in the human system. Systemic lupus erythematosus (SLE) is a heterogeneous complex disease which ensues due to the failure of the immune system to distinguish between self and non-self antigens, thus producing autoantibodies against DNA, RNA and proteins. Cancer, the other side of the same coin, results from an excessive proliferation of cells that evade immune regulation as a result of incompetent defense by T-cells, B-cells and macrophages...
January 1, 2017: Lupus
https://www.readbyqxmd.com/read/28119527/runx3-is-oncogenic-in-natural-killer-t-cell-lymphoma-and-is-transcriptionally-regulated-by-myc
#14
V Selvarajan, M Osato, G S S Nah, J Yan, C Tae-Hoon, Dc-C Voon, Y Ito, M F Ham, M Salto-Tellez, N Shimizu, S-N Choo, S Fan, W-J Chng, S-B Ng
RUNX3, runt-domain transcription factor, is a master regulator of gene expression in major developmental pathways. It acts as a tumor suppresser in many cancers but is oncogenic in certain tumors. We observed upregulation of RUNX3 mRNA and protein expression in nasal-type extranodal NK/T-cell lymphoma (NKTL) patient samples and NKTL cell lines compared to normal NK cells. RUNX3 silenced NKTL cells showed increased apoptosis and reduced cell proliferation. Potential binding sites for MYC were identified in the RUNX3 enhancer region...
January 25, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28088061/galectins-emerging-regulatory-checkpoints-linking-tumor-immunity-and-angiogenesis
#15
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
#16
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
#17
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, 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 12, 2017: Nature
https://www.readbyqxmd.com/read/28035916/the-paired-receptors-tigit-and-dnam-1-as-targets-for-therapeutic-antibodies
#18
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
#19
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
#20
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...
2017: Anticancer Research
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