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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/28205579/tim-3-inhibits-macrophage-control-of-listeria-monocytogenes-by-inhibiting-nrf2
#2
Zhiding Wang, Dejun Sun, Guojiang Chen, Ge Li, Shuaijie Dou, Renxi Wang, He Xiao, Chunmei Hou, Yan Li, Jiannan Feng, Beifen Shen, Gencheng Han
T cell immunoglobulin mucin-3 (Tim-3) is an immune checkpoint inhibitor and its dysregulation has been related to T cell tolerance and many immune disorders, such as tumors and infection tolerance. However, the physiopathology roles of Tim-3 in innate immunity remain elusive. Here, we demonstrate that Tim-3 inhibits macrophage phagocytosis of L. monocytogenes by inhibiting the nuclear erythroid 2-related factor 2 (Nrf2) signaling pathway and increases bacterial burden. Tim-3 signaling promotes Nrf2 degradation by increasing its ubiquitination and, as a result, decreasing its nuclear translocation...
February 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28197389/adaptive-resistance-to-anti-pd1-therapy-by-tim-3-upregulation-is-mediated-by-the-pi3k-akt-pathway-in-head-and-neck-cancer
#3
Gulidanna Shayan, Raghvendra Srivastava, Jing Li, Nicole Schmitt, Lawrence P Kane, Robert L Ferris
Programmed Death 1 (PD-1) and T cell Ig and mucin domain-3 protein (Tim-3) are immune checkpoint receptors that are expressed on tumor-infiltrating lymphocytes (TIL) in tumor-bearing mice and humans. As anti-PD-1 single agent response rates are only <20% in head and neck squamous cell carcinoma (HNSCC) patients, it is important to understand how multiple inhibitory checkpoint receptors maintain suppressed cellular immunity. One such receptor, Tim-3, activates downstream proliferative pathways through Akt/S6, and is highly expressed in dysfunctional TIL...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28197385/prognostic-and-predictive-aspects-of-the-tumor-immune-microenvironment-and-immune-checkpoints-in-malignant-pleural-mesothelioma
#4
Elly Marcq, Vasiliki Siozopoulou, Jorrit De Waele, Jonas van Audenaerde, Karen Zwaenepoel, Eva Santermans, Niel Hens, Patrick Pauwels, Jan P van Meerbeeck, Evelien L J Smits
Malignant pleural mesothelioma (MPM) is an aggressive cancer with a poor prognosis and an increasing incidence, for which novel therapeutic strategies are urgently required. Since the immune system has been described to play a presumed role in the protection against MPM, characterization of its tumor immune microenvironment (TME) and immune checkpoints can identify new immunotherapeutic targets and their predictive and/or prognostic value. To characterize the TME and the immune checkpoint expression profile, we performed immunohistochemistry (IHC) on formalin-fixed paraffin embedded (FFPE) tissue sections from 54 MPM patients (40 at time of diagnosis; 14 treated with chemotherapy)...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28179599/the-immune-dysfunction-in-ankylosing-spondylitis-patients
#5
Zhongliang Duan, Yuyan Gui, Cui Li, Jing Lin, Hans-Jürgen Gober, Juanxiu Qin, Dajin Li, Ling Wang
Ankylosing spondylitis (AS) is a spinal arthritic disease that is often associated with human leukocyte antigen (HLA)-B27, while only part of HLA-B27 carriers become AS patients. T cells have been reported to play an important role in the pathology of AS. T-cell immunoglobulin and mucin-domain-containing molecule 3 (Tim-3) and programmed death-1 (PD-1) have been known to negatively regulate the immune response. In this study, we used flow cytometry to analyze the immunological differences of peripheral bloodfrom 21 patients with AS, 22 cases who didn't have AS but were found to be HLA-B27 positive (HLA-B27+ group), and 16 normal healthy individuals (Healthy group)...
February 7, 2017: Bioscience Trends
https://www.readbyqxmd.com/read/28160999/-the-immune-checkpoints-how-does-it-work
#6
Clémence Granier, Vassili Soumelis, Marion Mandavit, Laure Gibault, Radia Belazzoug, Eléonore de Guillebon, Cécile Badoual, Eric Tartour, Hélène Roussel
Costimulatory molecules allow the full lymphocyte activation, whereas co-inhibitory molecules are negative counterparts that act as immune regulators, avoiding excessive response. In some context of chronic inflammation such as cancer, co-inhibitory immune checkpoint as CTLA-4, PD-1, Lag-3, Tim-3 can accumulate at the membrane of T cells leading to a state of anergy and therefore the loss of tumor growth control. Consequently, these immune checkpoints are considered as potential target in the treatment of cancer...
February 2017: Annales de Pathologie
https://www.readbyqxmd.com/read/28152393/molecular-cloning-characterization-and-expression-analysis-of-tim-3-and-galectin-9-in-the-woodchuck-model
#7
Yanan Liu, Junzhong Wang, Lu Wang, Baoju Wang, Shangqing Yang, Qin Wang, Jinzhuo Luo, Xuemei Feng, Xuecheng Yang, Yinping Lu, Michael Roggendorf, Mengji Lu, Dongliang Yang, Jia Liu
In recent years, a critical role for T cell immunoglobulin mucin domain 3 (Tim-3) and its ligand Galectin-9 (Gal-9) has emerged in infectious disease, autoimmunity and cancer. Manipulating this immune checkpoint may have immunotherapeutic potential and could represent an alternative approach for improving immune responses to viral infections and cancer. The woodchuck (Marmot monax) infected by woodchuck hepatitis virus (WHV) represents an informative animal model to study HBV infection and HCC. In the current study, the cDNA sequences of woodchuck Tim-3 and Gal-9 were cloned, sequenced and characterized...
March 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28151427/pd-1-modulates-regulatory-t-cell-homeostasis-during-low-dose-il-2-therapy
#8
Takeru Asano, Yusuke Meguri, Takanori Yoshioka, Yuriko Kishi, Miki Iwamoto, Makoto Nakamura, Yasuhisa Sando, Hideo Yagita, John Koreth, Haesook T Kim, Edwin P Alyea, Philippe Armand, Corey S Cutler, Vincent T Ho, Joseph H Antin, Robert J Soiffer, Yoshinobu Maeda, Mitsune Tanimoto, Jerome Ritz, Ken-Ichi Matsuoka
CD4+Foxp3+ regulatory T cells (Tregs) play a central role in the maintainance of immune tolerance after HSCT. We previously reported that low-dose IL-2 therapy increased circulating Tregs and improved clinical symptoms of chronic GVHD, however, the mechanisms which regulate Treg homeostasis during IL-2 therapy have not been well studied. To elucidate these regulatory mechanisms, we examined the role of inhibitory coreceptors on Tregs during IL-2 therapy in a murine model and in patients with chronic GVHD. Murine studies demonstrated that low-dose IL-2 selectively increased Treg and simultaneously enhanced the expression of Programmed death-1 (PD-1), especially on CD44(+)CD62L(+) central-memory Treg, while expression of other inhibitory molecules including CTLA-4, LAG-3 and TIM-3 remained stable...
February 1, 2017: Blood
https://www.readbyqxmd.com/read/28140445/virulence-dependent-induction-of-interleukin-10-producing-tolerogenic-dendritic-cells-by-mycobacterium-tuberculosis-impedes-optimal-th1-proliferation
#9
Hongmin Kim, Kee Woong Kwon, Woo Sik Kim, Sung Jae Shin
Mycobacterium tuberculosis (Mtb) inhibits optimal Th1 responses during infection. However, the precise mechanisms by which virulent Mtb limits Th1 responses remain unclear. Here, we infected dendritic cells (DCs) with the virulent Mtb strain H37Rv or the attenuated strain H37Ra to investigate the phenotypic and functional alterations in DCs and resultant T cell responses. H37Rv-infected DCs suppressed Th1 responses more strongly than H37Ra-infected DCs. Interestingly, H37Rv, but not H37Ra, impaired DC surface molecule (CD80, CD86 and MHC class II) expression due to prominent IL-10 production while augmenting the expression of tolerogenic molecules including PD-L1, CD103, Tim-3, and indoleamine 2,3-dioxygenase (IDO) on DCs in a multiplicity-of-infection-dependent manner...
January 31, 2017: Immunology
https://www.readbyqxmd.com/read/28132803/combined-blockade-of-tim-3-and-mek-inhibitor-enhances-the-efficacy-against-melanoma
#10
Yang Liu, Pengcheng Cai, Ning Wang, Qianwen Zhang, Fenghua Chen, Liang Shi, Yang Zhang, Lin Wang, Lihua Hu
Insights into the role of the mitogen-activated protein kinase (MAPK) pathway and immune checkpoints have led combined targeted therapy and immunotherapy to be a promising regimen. Trametinib, as a mitogen-activated extracellular signal-regulated kinase (MEK) inhibitor, has demonstrated effectiveness in patients with advanced melanoma. T cell immunoglobulin- and mucin-domain-containing molecule-3 (Tim-3), an immune checkpoint molecule, participates in multiple negative regulation of antitumor immunity. We for the first time to our knowledge reported the combination of trametinib and anti-Tim-3 monoclonal antibody (mAb) in treating B16-F10 melanoma mice...
January 26, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28112366/interference-with-tim-3-protein-expression-attenuates-the-invasion-of-clear-cell-renal-cell-carcinoma-and-aggravates-anoikis
#11
Muming Yu, Bin Lu, Yancun Liu, Ying Me, Lijun Wang, Hui Li
Tumor cells resistant to anoikis are considered to be candidates for metastasis. In the present study, the role of Tim‑3 in anoikis and its influence on the invasion of clear cell renal cell carcinoma (ccRCC) was investigated. Here, polyhydroxylethylmethacrylate (poly‑HEMA) was applied to two ccRCC cell lines, 786‑O and Caki‑2, to induce detachment from the extracellular matrix (ECM). Tim‑3 mRNA and protein expression levels were assayed by reverse transcription-quantitative polymerase chain reaction (RT‑qPCR) and western blot, respectively...
January 23, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28110884/tumor-antigen-specific-cd8-t-cells-are-negatively-regulated-by-pd-1-and-tim-3-in-human-gastric-cancer
#12
Xu Lu, Lin Yang, Daxing Yao, Xuan Wu, Jingpo Li, Xuesong Liu, Lijuan Deng, Caiting Huang, Yue Wang, Dan Li, Jingwei Liu
Cytotoxic CD8 T lymphocytes that are present in tumors and capable of recognizing tumor epitopes are nevertheless generally important in eliciting tumor rejection. NY-ESO-1 is a major target of CD8(+) T cell recognition in gastric cancer (GC) and is among the most immunogenic tumor antigens defined to date. Thus, identifying the immune escape mechanisms responsible for inducing tumor-specific CD8(+) T cell dysfunction may reveal effective strategies for immunotherapy. In an effort to understand in vivo tolerance mechanisms, we assessed the phenotype and function of NY-ESO-1-specific CD8(+) T cells derived from peripheral blood lymphocytes (PBLs) and tumor-associated lymphocytes (TALs) of GC patients...
January 5, 2017: Cellular Immunology
https://www.readbyqxmd.com/read/28110209/expansion-of-cd11b-ly-6c-myeloid-derived-suppressor-cells-mdscs-driven-by-galectin-9-attenuates-cvb3-induced-myocarditis
#13
Yingying Zhang, Mengying Zhang, Xueqin Li, Zongsheng Tang, Ling He, Kun Lv
Galectin-9 is known to play a role in the modulation of innate and adaptive immunity to ameliorate CVB3-induced myocarditis. In the present study, we found that galectin-9 induced the expansion of CD11b(+)Ly-6C(+) myeloid-derived suppressor cells (MDSCs) in the heart from CVB3-infected mice. Adoptive transfer of CD11b(+)Ly-6C(+) MDSCs significantly alleviated myocarditis accompanied by increased Th2 and Treg frequency and anti-inflammatory cytokines expression in the heart tissue. Moreover, Ly6C(+) MDSCs, but not Ly6G(+) cells, expressed Arg-1 and NOS2, and suppressed CD4(+) T cell proliferation in vitro in an Arg-1-dependent mechanism; an event that was reversed with treatment of either an Arg-1 inhibitor or addition of excess l-arginine...
March 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28104239/cd8-t-cells-of-chronic-hcv-infected-patients-express-multiple-negative-immune-checkpoints-following-stimulation-with-hcv-peptides
#14
Muttiah Barathan, Rosmawati Mohamed, Jamuna Vadivelu, Li Yen Chang, Ramachandran Vignesh, Jayalakshmi Krishnan, Panneer Sigamani, Alireza Saeidi, M Ravishankar Ram, Vijayakumar Velu, Marie Larsson, Esaki M Shankar
Hepatitis C virus (HCV)-specific CD4+ and CD8+ T cells are key to successful viral clearance in HCV disease. Accumulation of exhausted HCV-specific T cells during chronic infection results in considerable loss of protective functional immune responses. The role of T-cell exhaustion in chronic HCV disease remains poorly understood. Here, we studied the frequency of HCV peptide-stimulated T cells expressing negative immune checkpoints (PD-1, CTLA-4, TRAIL, TIM-3 and BTLA) by flow cytometry, and measured the levels of Th1/Th2/Th17 cytokines secreted by T cells by a commercial Multi-Analyte ELISArray™ following in vitro stimulation of T cells using HCV peptides and phytohemagglutinin (PHA)...
December 16, 2016: Cellular Immunology
https://www.readbyqxmd.com/read/28077434/transfer-of-allogeneic-cd4-t-cells-rescues-cd8-t-cells-in-anti-pd-l1-resistant-tumors-leading-to-tumor-eradication
#15
Ainhoa Arina, Theodore Karrison, Eva Galka, Karin Schreiber, Ralph R Weichselbaum, Hans Schreiber
Adoptively transferred CD8(+) T cells can stabilize the size of solid tumors over long periods of time by exclusively recognizing antigen cross-presented on tumor stroma. However, these tumors eventually escape T-cell-mediated growth control. The aim of this study was to eradicate such persistent cancers. In our model, the SIYRYYGL antigen is expressed by cancer cells that lack the MHC-I molecule K(b) needed for direct presentation, but the antigen is picked up and cross-presented by tumor stroma. A single injection of antigen-specific 2C CD8(+) T cells caused long-term inhibition of tumor growth, but without further intervention, tumors started to progress after approximately 3 months...
February 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28074937/circulating-t-lymphocyte-subsets-cytokines-and-immune-checkpoint-inhibitors-in-patients-with-bipolar-ii-or-major-depression-a-preliminary-study
#16
Wei Wu, Ya-Li Zheng, Li-Ping Tian, Jian-Bo Lai, Chan-Chan Hu, Peng Zhang, Jing-Kai Chen, Jian-Bo Hu, Man-Li Huang, Ning Wei, Wei-Juan Xu, Wei-Hua Zhou, Shao-Jia Lu, Jing Lu, Hong-Li Qi, Dan-Dan Wang, Xiao-Yi Zhou, Jin-Feng Duan, Yi Xu, Shao-Hua Hu
This study aimed to investigate the less known activation pattern of T lymphocyte populations and immune checkpoint inhibitors on immunocytes in patients with bipolar II disorder depression (BD) or major depression (MD). A total of 23 patients with BD, 22 patients with MD, and 20 healthy controls (HCs) were recruited. The blood cell count of T lymphocyte subsets and the plasma level of cytokines (IL-2, IL-4, IL-6, IL-10, TNF-α, and IFN-γ) were selectively investigated. The expression of T-cell immunoglobulin and mucin-domain containing-3 (TIM-3), programmed cell death protein 1 (PD-1) and its ligands, PD-L1 and PD-L2, on T lymphocytes and monocytes, was detected...
January 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28038383/co-expression-of-tim-3-and-ceacam1-promotes-t-cell-exhaustion-in-colorectal-cancer-patients
#17
Yang Zhang, Pengcheng Cai, Lei Li, Liang Shi, Panpan Chang, Tao Liang, Qianqian Yang, Yang Liu, Lin Wang, Lihua Hu
T-cell immunoglobulin domain and mucin domain-3(TIM-3) is an activation induced inhibitory molecule involved in immune tolerance and is recently reported to induce T cell exhaustion which is mediated by carcinoembryonic antigen cell adhesion molecule 1(CEACAM1), another well-known molecule expressed on activated T cells and involved in T cell inhibition. To investigate the expression of TIM-3 and CEACAM1 on circulating CD8(+) T cells and tumor infiltrating lymphocytes (TILs), 65 diagnosed colorectal cancer (CRC) patients and 38 healthy controls were enrolled in this study and the results showed that TIM-3 and CEACAM1 were both highly expressed on circulating CD8(+) T cells in CRC patients and elevated on TILs compared with paraneoplastic T cells...
February 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28035413/tim-3-is-upregulated-in-human-colorectal-carcinoma-and-associated-with-tumor-progression
#18
Muming Yu, Bin Lu, Yancun Liu, Ying Me, Lijun Wang, Peng Zhang
T cell immunoglobulin mucin-3 (Tim-3) has previously been implicated in the immune response and tumor biology. Colorectal carcinoma (CRC) is a malignancy, which is closely associated with inflammation. However, the role of Tim‑3 in the progression of CRC remains to be fully elucidated. The present study aimed to investigate the role of Tim‑3 in the progressive activities of human CRC. A total of 30 clinical CRC tissues and their adjacent tissues were collected. Slides from another 112 cases that underwent CRC surgical resection were also obtained...
February 2017: Molecular Medicine Reports
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
#19
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/27990849/investigation-of-t-cell-immunoglobulin-and-mucin-domain-containing-molecule-3-tim-3-polymorphisms-in-essential-thrombocythaemia-et
#20
Fuyan Han, Guanghai Wang, Yuantang Li, Wenjun Tian, Zhenfang Dong, Shiqing Cheng, Yiqing Liu, Teng Qu, Xiaoying Wang, Yong Wang, Bingchang Zhang, Ying Ju
OBJECTIVES: T-cell immunoglobulin- and mucin-domain-containing molecule-3 (TIM-3) is preferentially expressed on terminally differentiated Th1 cells and inhibits their IFN-γ production. It has been reported that chronic inflammation may be an important driving force for myeloproliferative neoplasms (MPNs). Therefore, we hypothesized that as an important inflammation regulator, TIM-3 may be involved in essential thrombocythaemia (ET). The goal of this study was to investigate whether the -1516G > T, -574G > T and +4259T > G single-nucleotide polymorphisms (SNPs) within the TIM-3 gene contribute to the genetic susceptibility of individuals to ET...
December 17, 2016: Hematology (Amsterdam, Netherlands)
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