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Cytotoxic t lymphocytes

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https://www.readbyqxmd.com/read/28719841/risk-of-treatment-related-mortality-in-cancer-patients-treated-with-ipilimumab-a-systematic-review-and-meta-analysis
#1
Sheng Zhang, Fei Liang, Wenfeng Li, Qing Wang
BACKGROUND: Fatal adverse events (FAEs) have been reported in cancer patients receiving ipilimumab-a monoclonal antibody against cytotoxic T-lymphocyte antigen-4, but the risk of treatment-related mortality is unknown. We performed a systematic review and meta-analysis of randomised controlled trials (RCTs) of ipilimumab to determine the overall risk of FAEs associated with ipilimumab. METHODS: We systematically searched MEDLINE, EMBASE, Cochrane CENTRAL, ClinicalTrial...
July 15, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28719552/immune-checkpoint-inhibitors-in-organ-transplant-patients
#2
Adam S Kittai, Hayden Oldham, Jeremy Cetnar, Matthew Taylor
Modulation of T-cell activity through blockade of coinhibitory molecules has revolutionized the treatment of various malignancies. Several immune checkpoint inhibitors are currently Food and Drug Administration approved which target various coinhibitory pathways including cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), programmed death 1 receptor (PD-1), and programmed cell death ligand-1. Clinical trials that lead to the Food and Drug Administration approval of these agents often excluded patients with an organ transplant...
July 17, 2017: Journal of Immunotherapy
https://www.readbyqxmd.com/read/28719055/endocrine-toxicity-of-immune-checkpoint-inhibitors-essential-crosstalk-between-endocrinologists-and-oncologists
#3
REVIEW
Frédéric Illouz, Claire Briet, Lucie Cloix, Yannick Le Corre, Nathalie Baize, Thierry Urban, Ludovic Martin, Patrice Rodien
Two types of immune checkpoint inhibitors, both antibodies that target cytotoxic T-lymphocyte antigen-4 and those that target programmed cell death-protein 1, have been approved for use in melanoma, non-small-cell lung cancer, and renal cell carcinoma as first-line or second-line therapy. Their adverse events are primarily regarded as immune-related adverse events. We felt it was important to pinpoint and discuss certain preconceptions or misconceptions regarding thyroid dysfunction, hypophysitis, and diabetes induced by immune checkpoint inhibitors...
July 18, 2017: Cancer Medicine
https://www.readbyqxmd.com/read/28718997/mesenchymal-stem-cell-derived-factors-immuno-modulatory-effects-and-therapeutic-potential
#4
REVIEW
Vladislav Volarevic, Marina Gazdic, Bojana Simovic Markovic, Nemanja Jovicic, Valentin Djonov, Nebojsa Arsenijevic
Stem cell-based therapy is considered to be a new hope in transplantation medicine. Among stem cells, mesenchymal stem cells (MSCs) are, due to their differentiation and immuno-modulatory characteristics, the most commonly used as therapeutic agents in the treatment of immune-mediated diseases. MSCs migrate to the site of inflammation and modulate immune response. The capacity of MSC to alter phenotype and function of immune cells are largely due to the production of soluble factors which expression varies depending on the pathologic condition to which MSCs are exposed...
July 18, 2017: BioFactors
https://www.readbyqxmd.com/read/28716985/two-microrna-signatures-for-malignancy-and-immune-infiltration-predict-overall-survival-in-advanced-epithelial-ovarian-cancer
#5
Ilya Korsunsky, Janaki Parameswaran, Iuliana Shapira, John Lovecchio, Andrew Menzin, Jill Whyte, Lisa Dos Santos, Sharon Liang, Tawfiqul Bhuiya, Mary Keogh, Houman Khalili, Cassandra Pond, Anthony Liew, Andrew Shih, Peter K Gregersen, Annette T Lee
MicroRNAs have been established as key regulators of tumor gene expression and as prime biomarker candidates for clinical phenotypes in epithelial ovarian cancer (EOC). We analyzed the coexpression and regulatory structure of microRNAs and their co-localized gene targets in primary tumor tissue of 20 patients with advanced EOC in order to construct a regulatory signature for clinical prognosis. We performed an integrative analysis to identify two prognostic microRNA/mRNA coexpression modules, each enriched for consistent biological functions...
July 17, 2017: Journal of Investigative Medicine: the Official Publication of the American Federation for Clinical Research
https://www.readbyqxmd.com/read/28716933/cortical-actin-recovery-at-the-immunological-synapse-leads-to-termination-of-lytic-granule-secretion-in-cytotoxic-t-lymphocytes
#6
Alex T Ritter, Senta M Kapnick, Sricharan Murugesan, Pamela L Schwartzberg, Gillian M Griffiths, Jennifer Lippincott-Schwartz
CD8(+) cytotoxic T lymphocytes (CTLs) eliminate virally infected cells through directed secretion of specialized lytic granules. Because a single CTL can kill multiple targets, degranulation must be tightly regulated. However, how CTLs regulate the termination of granule secretion remains unclear. Previous work demonstrated that centralized actin reduction at the immune synapse precedes degranulation. Using a combination of live confocal, total internal reflection fluorescence, and superresolution microscopy, we now show that, after granule fusion, actin recovers at the synapse and no further secretion is observed...
July 17, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28716895/ctla4-promotes%C3%A2-tyk2-stat3-dependent-b-cell-oncogenecity
#7
Andreas Herrmann, Christoph Lahtz, Toshikage Nagao, Joo Y Song, Wing C Chan, Heehyoung Lee, Chanyu Yue, Thomas Look, Ronja Muelfarth, Wenzhao Li, Kurt Jenkins, John Williams, Lihua E Budde, Stephen J Forman, Larry W Kwak, Thomas Blankenstein, Hua Yu
Cytotoxic T lymphocyte-associated antigen 4 (CTLA4) is a well-established immune checkpoint for antitumor immune responses. The pro-tumorigenic function of CTLA4 is believed to be limited to T cell inhibition by countering the activity of the T cell co-stimulating receptor CD28. However, as we demonstrate here, there are two additional roles for CTLA4 in cancer, including via CTLA4 overexpression in diverse B cell lymphomas and in melanoma-associated B cells. CTLA4-CD86 ligation recruited and activated the JAK family member Tyk2, resulting in STAT3 activation and expression of genes critical for cancer immunosuppression and tumor growth and survival...
July 17, 2017: Cancer Research
https://www.readbyqxmd.com/read/28715455/synthetic-melanin-bound-to-subunit-vaccine-antigens-significantly-enhances-cd8-t-cell-responses
#8
Antoine F Carpentier, Frédéric Geinguenaud, Thi Tran, Floraly Sejalon, Antoine Martin, Laurence Motte, Eric Tartour, Claire Banissi
Cytotoxic T-lymphocytes (CTLs) play a key role in immunity against cancer; however, the induction of CTL responses with currently available vaccines remains difficult. Because several reports have suggested that pigmentation and immunity might be functionally linked, we investigated whether melanin can act as an adjuvant in vaccines. Short synthetic peptides (8-35 amino acids long) containing T-cell epitopes were mixed with a solution of L-Dopa, a precursor of melanin. The mixture was then oxidized to generate nanoparticles of melanin-bound peptides...
2017: PloS One
https://www.readbyqxmd.com/read/28710916/systemic-immune-inflammation-index-and-circulating-t-cell-immune-index-predict-outcomes-in-high-risk-acral-melanoma-patients-treated-with-high-dose-interferon
#9
Jiayi Yu, Xiaowen Wu, Huan Yu, Siming Li, LiLi Mao, Zhihong Chi, Lu Si, Xinan Sheng, Chuanliang Cui, Jie Dai, Meng Ma, Huan Tang, Tianxiao Xu, Junya Yan, Yan Kong, Jun Guo
High-dose interferon alfa-2b (IFN-α-2b) improves the survival of patients with high-risk melanoma. We aimed to identify baseline peripheral blood biomarkers to predict the outcome of acral melanoma patients treated with IFN-α-2b. Pretreatment baseline parameters and clinical data were assessed in 226 patients with acral melanoma. Relapse-free survival (RFS) and overall survival (OS) were assessed using the Kaplan-Meier method, and multivariate Cox regression analyses were applied after adjusting for stage, lactate dehydrogenase (LDH), and ulceration...
July 12, 2017: Translational Oncology
https://www.readbyqxmd.com/read/28710313/ex-vivo-pd-l1-pd-1-pathway-blockade-reverses-dysfunction-of-circulating-cea-specific-t-cells-in-pancreatic-cancer-patients
#10
Yuan Chen, Shao-An Xue, Goran Hamid Mohammad, Stephen P Pereira, Emma Morris, Shahriar Behboudi
Carcinoembryonic antigen (CEA) is a candidate target for cellular immunotherapy of pancreatic cancer (PC). In this study, we have characterised the antigen-specific function of autologous cytotoxic T lymphocytes (CTL) specific for the HLA-A2 restricted peptide, pCEA691-699, isolated from the peripheral T cell repertoire of PC patients and sought to determine if ex vivo PD-L1 & TIM3 blockade could enhance CTL function. CD8(+) T cell lines were generated from peripheral blood mononuclear cells (PBMCs) of 18 HLA-A2(+) patients with PC and from 15 healthy controls...
July 14, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28708582/tumor-specific-hepatic-stellate-cells-thscs-induces-digr2-expression-in-dendritic-cells-to-inhibit-t-cells
#11
Yun-Hong Xia, Zhen Lu, Min Zhao, Wen-Ting Dai, Lu Ding, Li-Xia Hu, Guo-Lin Jiang
Tumor-specific hepatic stellate cells (tHSCs) contributes to tumorigenesis and progression of hepatocellular carcinoma (HCC). The potential function of tHSCs on dendritic cells (DCs) was studied here. We discovered that tHSCs co-culture induced upregulation of DIgR2 (dendritic cell-derived immunoglobulin receptor 2) in bone marrow-derived DCs (mDCs). Activation of MEK-ERK is required for DIgR2 expression in mDCs. MEK-ERK inhibitors or shRNA-mediated silence of MEK1/2 in mDCs inhibited tHSCs-induced DIgR2 expression...
July 5, 2017: Oncotarget
https://www.readbyqxmd.com/read/28708284/cd20-specific-immunoligands-engaging-nkg2d-enhance-%C3%AE-%C3%AE-t-cell-mediated-lysis-of-lymphoma-cells
#12
Matthias Peipp, Daniela Wesch, Hans-Heinrich Oberg, Sebastian Lutz, Anja Muskulus, Jan G J van de Winkel, Paul W H I Parren, Renate Burger, Andreas Humpe, Dieter Kabelitz, Martin Gramatzki, Christian Kellner
Human γδ T cells are innate-like T cells which are able to kill a broad range of tumor cells and thus may have potential for cancer immunotherapy. The activating receptor natural killer group 2 member D (NKG2D) plays a key role in regulating immune responses driven by γδ T cells. Here, we explored whether recombinant immunoligands consisting of a CD20 single-chain fragment variable (scFv) linked to a NKG2D ligand, either MHC class I chain-related protein A (MICA) or UL16 binding protein 2 (ULBP2), could be employed to engage γδ T cells for tumor cell killing...
July 14, 2017: Scandinavian Journal of Immunology
https://www.readbyqxmd.com/read/28706421/gastric-cancer-derived-heat-shock-protein-gp96-peptide-complex-enhances-dendritic-cell-activation
#13
Wen-Wen Lu, Hong Zhang, You-Ming Li, Feng Ji
AIM: To investigate the role of heat shock protein (HSP)-glycoprotein (gp)96 in dendritic cells (DCs) and lymphocytes induction in gastric cancer (GC). METHODS: Human GC cell lines KATOIII, MKN-28 and SGC-7901 were infected with adenovirus gp96 at a multiplicity of infection of 100. gp96-GC antigen peptide complexes were purified. MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay, lactate dehydrogenase (LDH) release assay and enzyme-linked immunosorbent assay were used to determine allo-reactive T cell stimulation, natural killer (NK) cell activity and expression of cytokines (such as interleukin (IL)-10, IL-12, interferon (IFN)-γ and tumor necrosis factor (TNF)-α), respectively...
June 28, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28706012/local-delivery-of-oncovex-mgm-csf-generates-systemic-anti-tumor-immune-responses-enhanced-by-cytotoxic-t-lymphocyte-associated-protein-blockade
#14
Achim K Moesta, Keegan Cooke, Julia Piasecki, Petia Mitchell, James B Rottman, Karen Fitzgerald, Jinghui Zhan, Becky Yang, Tiep Le, Brian Belmontes, Oluwatayo F Ikotun, Kim Merriam, Charles Glaus, Kenneth Ganley, David H Cordover, Andrea M Boden, Rafael Ponce, Courtney Beers, Pedro J Beltran
Talimogene laherparepvec, a new oncolytic immunotherapy, has been recently approved for the treatment of melanoma. Using a murine version of the virus we characterized local and systemic anti-tumor immune responses driving efficacy in murine syngeneic models.<br /><br />Experimental Design: The activity of talimogene laherparepvec was characterized against melanoma cell lines using an in vitro viability assay. Efficacy of OncoVEX(mGM-CSF) (talimogene laherparepvec with the mouse granulocyte-macrophage colony-stimulating factor transgene) alone or in combination with checkpoint blockade was characterized in A20 and CT-26 contralateral murine tumor models...
July 13, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28700505/sepsis-due-to-streptococcus-pneumoniae-associated-with-secondary-hemophagocytic-lymphohistiocytosis-in-a-splenectomized-patient-for-spherocytosis-a-case-report
#15
Victoria Birlutiu, Rares Mircea Birlutiu
RATIONALE: Hemophagocytic lymphohistiocytosis (HLH) is a syndrome that is characterized by an inappropriate hyperinflammatory immune response - primary, as a consequence of a genetic defect of NK cells and cytotoxic T lymphocytes or - secondary, in the progression of infections, rheumatic or autoimmune diseases, malignancies or metabolic diseases. PATIENT CONCERNS: We present the case of a secondary HLH due to Streptococcus pneumoniae infection in a splenectomised patient for spherocytosis, a 37-year-old patient who was splenectomised in childhood for spherocytosis, without immuneprophylaxis induced by antipneumococcal vaccine...
July 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28700351/association-between-lmp2-lmp7-genetic-variability-and-cancer-susceptibility-especially-among-asians-evidence-from-a-meta-analysis
#16
Yang Wu, Dong-Fang Liu, Jing-Jing Zhang, Xiao Li, Zi-Peng Lu, Guo-Dong Shi, Hao Yuan, Yu-Gang Ge, Peng-Fei Wu, Yan Wang, Kui-Rong Jiang, Yi Miao
Low molecular mass protein (LMP) gene performs a critical role in the foreign antigen processing machine via the major histocompatibility complex-I (MHC-I) complex CD8+ cytotoxic T lymphocytes (CTL) pathway. Recent studies have reported the association of LMP2-60 G>A (rs17587) and LMP7-145 C>A (rs2071543) polymorphisms with various types of cancers, but the outcomes remained inconsistent. To obtain a reliable conclusion, we summarized available data and conducted a meta-analysis involving a total of 19 published studies...
June 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28700031/inhibitory-effect-of-the-pseudobrickellia-brasiliensis-spreng-r-m-king-h-rob-aqueous-extract-on-human-lymphocyte-proliferation-and-ifn-%C3%AE-and-tnf-%C3%AE-production-in-vitro
#17
V G Almeida, B A Avelar-Freitas, M G Santos, L A Costa, T J Silva, W F Pereira, M L L Amorim, C F F Grael, L E Gregório, E Rocha-Vieira, G E A Brito-Melo
Pseudobrickellia brasiliensis (Asteraceae) is a plant commonly known as arnica-do-campo and belongs to the native flora of the Brazilian Cerrado. The alcoholic extract of the plant has been used as an anti-inflammatory agent in folk medicine, but the biological mechanism of action has not been elucidated. The present study evaluated the composition of P. brasiliensis aqueous extract and its effects on pro-inflammatory cytokine production and lymphocyte proliferation. The extracts were prepared by sequential maceration of P...
July 10, 2017: Brazilian Journal of Medical and Biological Research, Revista Brasileira de Pesquisas Médicas e Biológicas
https://www.readbyqxmd.com/read/28699667/mantle-cell-lymphoma-2017-update-on-diagnosis-risk-stratification-and-clinical-management
#18
Julie M Vose
DISEASE OVERVIEW: Mantle cell lymphoma (MCL) is a non-Hodgkin lymphoma characterized by involvement of the lymph nodes, spleen, blood and bone marrow with a short remission duration to standard therapies and a median overall survival (OS) of 4-5 years. DIAGNOSIS: Diagnosis is based on lymph node, bone marrow, or tissue morphology of centrocytic lymphocytes, small cell type, or blastoid variant cells. A chromosomal translocation t (11:14) is the molecular hallmark of MCL, resulting in the overexpression of cyclin D1...
August 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/28697066/viral-induced-modulation-of-multiple-checkpoint-proteins-in-cancers
#19
Gerard J Nuovo, Virginia A Folcik, Cynthia Magro
Therapy with checkpoint inhibitors represents a major advance in cancer treatment. The purpose of this study was to examine the expression patterns of the checkpoint proteins programmed death ligand 1 (PD L1), PD L2, indoleamine 2,3-dioxygenase 1 (IDO1), and cytotoxic T-lymphocyte antigen 4 (CTLA4) in cancers including those associated with viral infections. Normal, noninflamed tissues rarely express checkpoint proteins with exceptions including the placenta and stomach. Expression of PD L1 was noted in 30%, PD L2 in 18%, IDO1 in 13%, and CTLA4 in 14% of 333 nonviral malignancies including endometrial, ovarian, lung, and breast cancers...
July 2017: Applied Immunohistochemistry & Molecular Morphology: AIMM
https://www.readbyqxmd.com/read/28697053/postoperative-adjuvant-therapy-for-resectable-pancreatic-cancer-with-gemcitabine-and-adoptive-immunotherapy
#20
Hiroto Matsui, Shoichi Hazama, Kazuhiko Sakamoto, Yoshitaro Shindo, Shinsuke Kanekiyo, Masao Nakashima, Satoshi Matsukuma, Yoshihiro Tokuhisa, Michihisa Iida, Nobuaki Suzuki, Kiyoshi Yoshimura, Shigeru Takeda, Tomio Ueno, Shigefumi Yoshino, Masaaki Oka, Hiroaki Nagano
OBJECTIVES: We previously described adoptive immunotherapy (AIT) with cytotoxic T lymphocytes (CTLs) stimulated by the mucin 1 (MUC1)-expressing human pancreatic cancer cell line YPK-1 (MUC1-CTLs) and demonstrated that MUC1-CTLs might prevent liver metastasis. In the present study, we combined gemcitabine (GEM) and AIT for the treatment of pancreatic cancer. METHODS: A total of 43 patients who underwent radical pancreatectomy received treatment with MUC1-CTLs and GEM...
July 11, 2017: Pancreas
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