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https://www.readbyqxmd.com/read/28213366/tumor-infiltrating-and-peripheral-blood-t-cell-immunophenotypes-predict-early-relapse-in-localized-clear-cell-renal-cell-carcinoma
#1
Nicolas A Giraldo, Etienne Becht, Yann Vano, Florent Petitprez, Laetitia Lacroix, Pierre Validire, Rafael Sanchez-Salas, Alexandre Ingels, Stephane Marie Oudard, Audrey Moatti, Bénédicte Buttard, Sarah Bourras, Claire Germain, Xavier Cathelineau, Wolf-Herman Fridman, Catherine Sautes-Fridman
PURPOSE: The efficacy of PD-1 Checkpoint Blockade (ChB) as adjuvant therapy in localized clear cell Renal Cell Carcinoma (ccRCC) is currently unknown. The identification of tumor microenvironment (TME) prognostic biomarkers in this setting may help to define which patients could benefit from ChB and to uncover new therapeutic targets. EXPERIMENTAL DESIGN: We performed multiparametric flow cytometry immunophenotypic analysis of T cells isolated from tumor tissue (TIL), adjacent non-malignant renal tissue (RIL) and peripheral blood (PBL), in a cohort of patients (n=40) with localized ccRCC...
February 17, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28186088/current-status-of-immunotherapy-for-gastrointestinal-stromal-tumor
#2
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/28159737/stem-and-progenitor-cell-alterations-in-myelodysplastic-syndromes
#3
Aditi Shastri, Britta Will, Ulrich Steidl, Amit Verma
Recent studies have demonstrated that myelodysplastic syndromes (MDS) arise from a small population of disease initiating hematopoietic stem cells (HSCs) that persist and expand through conventional therapies and are major contributors to disease progression and relapse. MDS stem and progenitor cells are characterized by key founder and driver mutations and are enriched for cytogenetic alterations. Quantitative alterations in stem and progenitor numbers are also seen in a stage specific manner in human MDS samples as well as in murine models of the disease...
February 3, 2017: Blood
https://www.readbyqxmd.com/read/28158245/protein-kinase-c-theta-is-required-for-efficient-induction-of-il-10-secreting-t-cells
#4
Graham J Britton, Ruth E Mitchell, Bronwen R Burton, David C Wraith
Secretion of interleukin-10 (IL-10) by CD4+ T cells is an essential immunoregulatory mechanism. The work presented here assesses the role of the signaling molecule protein kinase C theta (PKCθ) in the induction of IL-10 expression in CD4+ T cells. Using wildtype and PKCθ-deficient Tg4 T cell receptor transgenic mice, we implemented a well-described protocol of repeated doses of myelin basic protein (MBP)Ac1-9[4Y] antigen to induce Tr1-like IL-10+ T cells. We find that PKCθ is required for the efficient induction of IL-10 following antigen administration...
2017: PloS One
https://www.readbyqxmd.com/read/28103502/tim3-gal9-interactions-between-t-cells-and-monocytes-result-in-an-immunosuppressive-feedback-loop-that-inhibits-th1-responses-in-osteosarcoma-patients
#5
Xiuzhong Li, Yanqing Chen, Xu Liu, Jin Zhang, Xu He, Guodong Teng, Dazhi Yu
The Tim3/Gal9 pathway is associated with immunosuppression and worse clinical outcome in multiple cancers. To illustrate the specific mechanism of Tim3/Gal9 interaction in osteosarcoma, we examined expression, function, and regulation of Tim3/Gal9 in various cells from osteosarcoma patients. Data showed that CD4(+) T cells, CD8(+) T cells, and monocytes from both peripheral blood and tumor of osteosarcoma patients contained high frequencies of Tim3(+) cells, while the Gal9 expression was primarily found in regulatory T cells (Tregs) from osteosarcoma patients and was elevated compared to that in non-cancer controls...
March 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28102051/t-cell-immunoglobulin-mucin-3-blockade-drives-an-antitumor-immune-response-in-head-and-neck-cancer
#6
Jian-Feng Liu, Si-Rui Ma, Liang Mao, Lin-Lin Bu, Guang-Tao Yu, Yi-Cun Li, Cong-Fa Huang, Wei-Wei Deng, Ashok B Kulkarni, Wen-Feng Zhang, Zhi-Jun Sun
T-cell immunoglobulin mucin 3 (TIM3) contributes to immune suppression during progression of many cancers, but the precise role of TIM3 in head and neck squamous cell carcinoma (HNSCC) is not clearly understood. In this study, we report that TIM3 expression was significantly up-regulated in patients with HNSCC and associated with lymph node metastasis. Additionally, TIM3 expression was increased in patients with recurrent HNSCC and patients with preradiotherapy or prechemotherapy. We also characterized CD8(+) T cells and CD11b(+) CD33(+) myeloid-derived suppressor cells (MDSCs) in human HNSCC, and found that their expression was positively correlated with TIM3 expression...
February 2017: Molecular Oncology
https://www.readbyqxmd.com/read/28033288/immune-checkpoint-proteins-pd-1-and-tim-3-are-both-highly-expressed-in-liver-tissues-and-correlate-with-their-gene-polymorphisms-in-patients-with-hbv-related-hepatocellular-carcinoma
#7
Zhu Li, Na Li, Fang Li, Zhihua Zhou, Jiao Sang, Yanping Chen, Qunying Han, Yi Lv, Zhengwen Liu
Immune checkpoint proteins programmed death-1 (PD-1) and T-cell immunoglobulin domain and mucin domain containing molecule-3 (TIM-3) expression and their gene polymorphisms have separately been shown to be associated with hepatitis B virus (HBV) infection and hepatocellular carcinoma (HCC). This study simultaneously examined PD-1 and TIM-3 expression in liver tissues and PD1 and TIM3 polymorphisms and analyzed their correlations in 171 patients with HBV-related HCC and 34 patients with HBV-related cirrhosis...
December 2016: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28003483/adenovirus-serotype-5-vaccination-results-in-suboptimal-cd4-t-helper-1-responses-in-mice
#8
Junghwa Lee, Masao Hashimoto, Se Jin Im, Koichi Araki, Hyun-Tak Jin, Carl W Davis, Bogumila T Konieczny, Gregory A Spies, M Juliana McElrath, Rafi Ahmed
Adenovirus serotype 5 (Ad5) is one of the most widely used viral vectors and is known to generate potent T cell responses. While many previous studies have characterized Ad5-induced CD8 T cell responses, there is a relative lack of detailed studies that have analyzed CD4 T cells elicited by Ad5 vaccination. Here, we immunized mice with Ad5 vectors encoding lymphocytic choriomeningitis virus (LCMV) glycoprotein (GP) and examined GP-specific CD4 T cell responses elicited by Ad5 vectors and compared them to those induced by an acute LCMV infection...
March 1, 2017: Journal of Virology
https://www.readbyqxmd.com/read/27846431/increased-tim3-cd8-t-cells-in-myelodysplastic-syndrome-patients-displayed-less-perforin-and-granzyme-b-secretion-and-higher-cd95-expression
#9
Jinglian Tao, Lijuan Li, Yingshuai Wang, Rong Fu, Huaquan Wang, Zonghong Shao
T cell immunoglobulin and mucin domain 3(TIM3) is a negative regulator of cellular immunity and it is highly expressed on CD8+T cells in persistent viral infection and cancer setting as report. However, how TIM3 expressed on CD8+T cells in myelodysplastic syndrome (MDS), that is a malignant disorder, has not been clarified. Here, decreased CD8+T cells, less IFN-γ secretion in CD8+T cells and increased TIM3 on CD8+T cells had been seen. Increased TIM3+CD8+T cells with lower perforin and granzyme B expression and higher CD95 expression in MDS patients had been observed...
November 2, 2016: Leukemia Research
https://www.readbyqxmd.com/read/27827824/plasma-biomarkers-of-risk-for-death-in-a-multicenter-phase-3-trial-with-uniform-transplant-characteristics-post-allogeneic-hct
#10
Mohammad Abu Zaid, Juan Wu, Cindy Wu, Brent R Logan, Jeffrey Yu, Corey Cutler, Joseph H Antin, Sophie Paczesny, Sung Won Choi
A phase 3 clinical trial (BMT CTN 0402) comparing tacrolimus/sirolimus (Tac/Sir) vs tacrolimus/methotrexate (Tac/Mtx) as graft-versus-host disease (GVHD) prophylaxis after matched-related allogeneic hematopoietic cell transplantation (HCT) recently showed no difference between study arms in acute GVHD-free survival. Within this setting of a prospective, multicenter study with uniform GVHD prophylaxis, conditioning regimen, and donor source, we explored the correlation of 10 previously identified biomarkers with clinical outcomes after allogeneic HCT...
January 12, 2017: Blood
https://www.readbyqxmd.com/read/27754489/in-silico-aptamer-docking-studies-from-a-retrospective-validation-to-a-prospective-case-study-tim3-aptamers-binding
#11
Obdulia Rabal, Fernando Pastor, Helena Villanueva, Mario M Soldevilla, Sandra Hervas-Stubbs, Julen Oyarzabal
Complementing Systematic Evolution of Ligands by EXponential Enrichment (SELEX) technologies with in silico prediction of aptamer binders has attracted a lot of interest in the recent years. We propose a workflow involving 2D structure prediction, 3D RNA modeling using Rosetta and docking to the target protein with 3dRPC for: (i) prediction of the binding mode of our two previously reported potent (Kd < 50 nmol/l) murine TIM3 aptamers, and (ii) the prioritization of TIM3 aptamers that were enriched in the SELEX workflow...
October 18, 2016: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/27744729/epigallocatechin-3-gallate-prevents-triptolide-induced-hepatic-injury-by-restoring-the-th17-treg-balance-in-mice
#12
Shu-Jing Yu, Rong Jiang, Ying Z Mazzu, Cai-Bing Wei, Zong-Liang Sun, Yu-Zhen Zhang, Lian-Di Zhou, Qi-Hui Zhang
Drug-induced liver injury (DILI) is the most common cause of acute liver failure. Disruption of the Th17/Treg balance can lead to hepatic inflammation, which causes the main symptoms of DILI. Here we investigate the protective mechanisms of (-)-Epigallocatechin-3-gallate (EGCG) on triptolide (TP)-induced DILI that shows the Th17/Treg imbalance. Pretreatment with EGCG (5[Formula: see text]mg/kg) for 10 days before TP (0.5[Formula: see text]mg/kg) administration in mice significantly reduced the increased alanine aminotransferase (ALT) level ([Formula: see text]) induced by TP treatment...
2016: American Journal of Chinese Medicine
https://www.readbyqxmd.com/read/27549193/comprehensive-analyses-of-tumor-immunity-implications-for-cancer-immunotherapy
#13
Bo Li, Eric Severson, Jean-Christophe Pignon, Haoquan Zhao, Taiwen Li, Jesse Novak, Peng Jiang, Hui Shen, Jon C Aster, Scott Rodig, Sabina Signoretti, Jun S Liu, X Shirley Liu
BACKGROUND: Understanding the interactions between tumor and the host immune system is critical to finding prognostic biomarkers, reducing drug resistance, and developing new therapies. Novel computational methods are needed to estimate tumor-infiltrating immune cells and understand tumor-immune interactions in cancers. RESULTS: We analyze tumor-infiltrating immune cells in over 10,000 RNA-seq samples across 23 cancer types from The Cancer Genome Atlas (TCGA). Our computationally inferred immune infiltrates associate much more strongly with patient clinical features, viral infection status, and cancer genetic alterations than other computational approaches...
August 22, 2016: Genome Biology
https://www.readbyqxmd.com/read/27544230/clinical-significance-of-tim3-positive-t-cell-subsets-in-patients-with-multiple-sclerosis
#14
Xuemei Feng, Juan Feng
The present study evaluated associations between the percentages of T cell immunoglobulin and mucin domain 3 (Tim3)-positive T cells and related cytokines and multiple sclerosis (MS). We collected peripheral blood samples from 30 MS patients and 30 healthy controls. Flow cytometry was used to determine the proportions of CD3(+)Tim3(+), CD4(+)Tim3(+), and CD4(+)CD25(+)Tim3(+) in peripheral blood mononuclear cells (PBMCs) and related cell subsets. The serum concentrations of galectin-9, IL-17, and IFN-γ also were determined using enzyme-linked immunosorbent assays (ELISA)...
December 2016: Journal of Clinical Neuroscience: Official Journal of the Neurosurgical Society of Australasia
https://www.readbyqxmd.com/read/27515948/plasma-levels-of-galectin-9-reflect-disease-severity-in-malaria-infection
#15
Bindongo P P Dembele, Haorile Chagan-Yasutan, Toshiro Niki, Yugo Ashino, Noppadon Tangpukdee, Egawa Shinichi, Srivicha Krudsood, Shigeyuki Kano, Toshio Hattori
BACKGROUND: Galectin-9 (Gal-9) is a β-galactoside-binding lectin that interacts with sugar moieties on glycoproteins and glycolipids of cells and pathogens. Gal-9 is known as an immune modulator that induces cell death via interaction with T cell immunoglobulin and mucin domain-3 (Tim3), a co-inhibitory receptor, and it inhibits production of several pro-inflammatory cytokines (TNF, IL-6 and IL-1α) and enhances production of IL-10. To understand the immune pathology of malaria, the Gal-9 in plasma was measured...
August 11, 2016: Malaria Journal
https://www.readbyqxmd.com/read/27511728/suppression-of-glut1-and-glucose-metabolism-by-decreased-akt-mtorc1-signaling-drives-t-cell-impairment-in-b-cell-leukemia
#16
Peter J Siska, Gerritje J W van der Windt, Rigel J Kishton, Sivan Cohen, William Eisner, Nancie J MacIver, Arnon P Kater, J Brice Weinberg, Jeffrey C Rathmell
Leukemia can promote T cell dysfunction and exhaustion that contributes to increased susceptibility to infection and mortality. The treatment-independent mechanisms that mediate leukemia-associated T cell impairments are poorly understood, but metabolism tightly regulates T cell function and may contribute. In this study, we show that B cell leukemia causes T cells to become activated and hyporesponsive with increased PD-1 and TIM3 expression similar to exhausted T cells and that T cells from leukemic hosts become metabolically impaired...
September 15, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27490575/highly-immunogenic-virally-vectored-t-cell-vaccines-cannot-overcome-subversion-of-the-t-cell-response-by-hcv-during-chronic-infection
#17
Leo Swadling, John Halliday, Christabel Kelly, Anthony Brown, Stefania Capone, M Azim Ansari, David Bonsall, Rachel Richardson, Felicity Hartnell, Jane Collier, Virginia Ammendola, Mariarosaria Del Sorbo, Annette Von Delft, Cinzia Traboni, Adrian V S Hill, Stefano Colloca, Alfredo Nicosia, Riccardo Cortese, Paul Klenerman, Antonella Folgori, Eleanor Barnes
An effective therapeutic vaccine for the treatment of chronic hepatitis C virus (HCV) infection, as an adjunct to newly developed directly-acting antivirals (DAA), or for the prevention of reinfection, would significantly reduce the global burden of disease associated with chronic HCV infection. A recombinant chimpanzee adenoviral (ChAd3) vector and a modified vaccinia Ankara (MVA), encoding the non-structural proteins of HCV (NSmut), used in a heterologous prime/boost regimen induced multi-specific, high-magnitude, durable HCV-specific CD4+ and CD8+ T-cell responses in healthy volunteers, and was more immunogenic than a heterologous Ad regimen...
August 2, 2016: Vaccines
https://www.readbyqxmd.com/read/27458246/antitumor-effect-of-programmed-death-1-pd-1-blockade-in-humanized-the-nog-mhc-double-knockout-mouse
#18
Tadashi Ashizawa, Akira Iizuka, Chizu Nonomura, Ryota Kondou, Chie Maeda, Haruo Miyata, Takashi Sugino, Koichi Mitsuya, Nakamasa Hayashi, Yoko Nakasu, Kouji Maruyama, Ken Yamaguchi, Ikumi Katano, Mamoru Ito, Yasuto Akiyama
PURPOSE: Humanized mouse models using NOD/Shi-scid-IL2rγ(null) (NOG) and NOD/LtSz-scid IL2rγ(null) (NSG) mouse are associated with several limitations, such as long incubation time for stem cell engraftment and the development of xenograft versus host disease in mice injected with peripheral blood mononuclear cells (PBMCs). To solve problems, we used humanized major histocompatibility class I- and class II-deficient NOG mice (referred to as NOG-dKO) to evaluate the antitumor effect of anti-programmed death-1 (PD-1) antibody...
January 1, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27447564/mir-28-modulates-exhaustive-differentiation-of-t-cells-through-silencing-programmed-cell-death-1-and-regulating-cytokine-secretion
#19
Qing Li, Nathan Johnston, Xiufen Zheng, Hongmei Wang, Xusheng Zhang, Dian Gao, Weiping Min
T cell exhaustion is a state of T cell dysfunction that arises during many cancer. miRNAs are one of major gene regulators which result in translational inhibition and/or mRNA degradation. We hypothesized that miRNAs exist that can silence PD1 and act as a modulator in vitro to revert exhaustive status of T cells. We demonstrated that the exhausted T cells with inhibitory receptors (IRs) are significantly increased in the melanoma-bearing mice. Meanwhile, the differentiated miRNA profiles in PD1+ exhaustive T cells were identified using a miRNA array; 11 miRNAs were observed with significant altered levels in the exhausted T cells isolated from melanoma-bearing mice...
August 16, 2016: Oncotarget
https://www.readbyqxmd.com/read/27424989/expression-of-microrna-mir-34a-inhibits-leukemia-stem-cells-and-its-metastasis
#20
S Wang, T Wang, M-Z Li, X-L Cheng, X-L Li
OBJECTIVE: To study the expression profile and role of microRNA miR-34a in Leukemia stem cells (LSC) and during its metastasis. We examined upon the enforced expression of miR-34a in TIM3 positive leukemia stem cells and study the impact of leukemia stem cells and its metastasis. PATIENTS AND METHODS: Samples were collected from acute myeloid leukemia (AML) children along with controls. Immunohistochemistry analysis was performed with TIM3 antibody followed by Sorting of TIM3 positive cells by flow cytometry and the expression level of miR-34a was quantified by qRT-PCR assay...
July 2016: European Review for Medical and Pharmacological Sciences
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