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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
#1
Ainhoa Arina, Theodore G 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...
January 11, 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
#2
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
#3
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
#4
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
#5
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
#6
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)
https://www.readbyqxmd.com/read/27990323/impaired-functional-responses-in-follicular-lymphoma-cd8-tim-3-t-lymphocytes-following-tcr-engagement
#7
Pauline Gravelle, Catherine Do, Camille Franchet, Sabina Mueller, Lucie Oberic, Loïc Ysebaert, Luigi Maria Larocca, Stefan Hohaus, Marie-Noëlle Calmels, François-Xavier Frenois, Robert Kridel, Randy D Gascoyne, Guy Laurent, Pierre Brousset, Salvatore Valitutti, Camille Laurent
Upregulation of T cell immunoglobulin-3 (TIM-3) has been associated with negative regulation of the immune response in chronic infection and cancer, including lymphoma. Here, we investigated the possible correlation between TIM-3 expression by ex vivo cytotoxic T cells (CTL) from follicular lymphoma (FL) biopsies and their functional unresponsiveness that could limit the favorable impact of CTL on disease progression. We report a high percentage of CD8(+)TIM-3(+)T cells in lymph nodes of FL patients. When compared to their CD8(+)TIM-3(-) counterparts, CD8(+)TIM-3(+) T cells exhibited defective cytokine production following TCR engagement...
2016: Oncoimmunology
https://www.readbyqxmd.com/read/27979840/early-effector-t-lymphocytes-coexpress-multiple-inhibitory-receptors-in-primary-non-small-cell-lung-cancer
#8
Elena Tassi, Giulia Grazia, Claudia Vegetti, Ilaria Bersani, Giulia Bertolini, Alessandra Molla, Paola Baldassari, Francesca Andriani, Luca Roz, Gabriella Sozzi, Ugo Pastorino, Roberta Mortarini, Andrea Anichini
Clinical efficacy of PD-1/PD-L1 targeting relies upon the reactivation of tumor-specific but functionally impaired PD-1+ T cells present before therapy. Thus, analyzing early stage primary tumors may reveal the presence of T cells that are not yet functionally impaired. In this study, we report that activated (HLA-DR+) T cells with an effector memory (TEM) profile are enriched in such lesions. Tumor-infiltrating lymphocytes (TIL) coexpressed PD-1 with the inhibitory receptors TIM-3, CTLA-4, LAG-3 and TIGIT, but also displayed a recently activated, non-exhausted phenotype...
December 15, 2016: Cancer Research
https://www.readbyqxmd.com/read/27917276/preparation-and-characterization-of-a-novel-nanobody-against-t-cell-immunoglobulin-and-mucin-3-tim-3
#9
Vida Homayouni, Mazdak Ganjalikhani-Hakemi, Abbas Rezaei, Hossein Khanahmad, Mahdi Behdani, Fatemeh Kazemi Lomedasht
OBJECTIVES: As T-cell immunoglobulin and mucin domain 3 (TIM-3) is an immune regulatory molecule; its blocking or stimulating could alter the pattern of immune response towards a desired condition. Based on the unique features of nanobodies, we aimed to construct an anti-TIM-3 nanobody as an appropriate tool for manipulating immune responses for future therapeutic purposes. MATERIALS AND METHODS: We immunized a camel with TIM-3 antigen and then, synthesized a VHH phage: mid library from its B cell's transcriptome using nested PCR...
November 2016: Iranian Journal of Basic Medical Sciences
https://www.readbyqxmd.com/read/27911104/upregulation-of-t-cell-immunoglobulin-and-mucin-domain-containing-3-tim-3-in-monocytes-macrophages-associates-with-gastric-cancer-progression
#10
Zhenxin Wang, Ni Yin, Zixiang Zhang, Yi Zhang, Guangbo Zhang, Weichang Chen
T-cell immunoglobulin and mucin-domain containing-3 (Tim-3) is an important immune regulatory molecule in cancer immune system. However, expression and function of Tim-3 in monocytes/macrophages in cancer progression mainly remain unclear. In this study, we analyzed Tim-3 levels in peripheral blood mononuclear cells (PBMCs) from 62 gastric cancer patients and 45 healthy controls using flow cytometry and then associated Tim-3 levels with clinical pathological data from patients. We found Tim-3 level was significantly upregulated in monocytes from gastric cancer patients compared with those from healthy controls, and that upregulated Tim-3 levels associated with depth of tumor invasion and tumor lymph node metastasis and advanced clinical stages of gastric cancer patients...
December 2, 2016: Immunological Investigations
https://www.readbyqxmd.com/read/27881010/down-regulated-expression-of-tim-3-promotes-invasion-and-metastasis-of-colorectal-cancer-cells
#11
Q Y Sun, C H Qu, J Q Liu, P Zhang, J Yao
To explore how Tim-3 is expressed and how its expression influences invasion and metastasis of colorectal cancer (CRC) cells. A total of 188 CRC patients were prospectively collected for this study. Meanwhile, 135 normal controls were incorporated during the same period. Intestinal samples of the CRC radical cancerous tissues, paracancerous tissues ( 5.0 cm beyond the cancer tissue) were collected for the following experiment. Furthermore, peripheral venous blood samples (10 ml) were collected from each subject...
November 24, 2016: Neoplasma
https://www.readbyqxmd.com/read/27872087/tim-3-expression-on-tumor-infiltrating-pd-1-cd8-t-cells-correlates-with-poor-clinical-outcome-in-renal-cell-carcinoma
#12
Clémence Granier, Charles Dariane, Pierre Combe, Virginie Verkarre, Saik Urien, Cecile Badoual, Hélène Roussel, Marion Mandavit, Patrice Ravel, Mathilde Sibony, Lucie Biard, Camelia Radulescu, Emeline Vinatier, Nadine Benhamouda, Michael Peyromaure, Stephane Oudard, Arnaud Méjean, Marc Olivier Timsit, Alain Gey, Eric Tartour
Inhibitory receptors expressed by T cells mediate tolerance to tumor antigens with coexpression of these receptors exacerbating this dysfunctional state. Using the VectraR automated multiparametric immunofluorescence technique, we quantified intratumoral CD8+T cells coexpressing the inhibitory receptors PD-1 and Tim-3 from patients with renal cell carcinoma (RCC). A second validation cohort measured the same parameters by cytometry. The percentage of tumor-infiltrating CD8+T cells coexpressing PD-1 and Tim-3 correlated with an aggressive phenotype and a larger tumor size at diagnosis...
November 21, 2016: Cancer Research
https://www.readbyqxmd.com/read/27856426/cytotoxic-t-cells-in-pd-l1-positive-malignant-pleural-mesotheliomas-are-counterbalanced-by-distinct-immunosuppressive-factors
#13
Mark M Awad, Robert E Jones, Hongye Liu, Patrick H Lizotte, Elena V Ivanova, Meghana Kulkarni, Grit S Herter-Sprie, Xiaoyun Liao, Abigail A Santos, Mark A Bittinger, Lauren Keogh, Shohei Koyama, Christina Almonte, Jessie M English, Julianne Barlow, William G Richards, David A Barbie, Adam J Bass, Scott J Rodig, F Stephen Hodi, Kai W Wucherpfennig, Pasi A Jänne, Lynette M Sholl, Peter S Hammerman, Kwok-Kin Wong, Raphael Bueno
PD-L1 immunohistochemical staining does not always predict whether a cancer will respond to treatment with PD-1 inhibitors. We sought to characterize immune cell infiltrates and the expression of T-cell inhibitor markers in PD-L1-positive and PD-L1-negative malignant pleural mesothelioma samples. We developed a method for immune cell phenotyping using flow cytometry on solid tumors that have been dissociated into single-cell suspensions and applied this technique to analyze 43 resected malignant pleural mesothelioma specimens...
December 2016: Cancer Immunology Research
https://www.readbyqxmd.com/read/27853635/tumor-infiltrating-tim-3-t-cells-proliferate-avidly-except-when-pd-1-is-co-expressed-evidence-for-intracellular-cross-talk
#14
Jing Li, Gulidanna Shayan, Lyndsay Avery, Hyun-Bae Jie, Neil Gildener-Leapman, Nicole Schmitt, Bin Feng Lu, 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 highly expressed on tumor infiltrating T lymphocytes (TIL). PD-1 inhibits T cell activation and type-1 T cell responses, while Tim-3 is proposed to mark more extensively exhausted cells, although the mechanisms underlying Tim-3 function are not clear. Trials of anti-PD-1 therapy have identified a large subset of non-responder patients, likely due to expression of alternative checkpoint molecules like Tim-3...
2016: Oncoimmunology
https://www.readbyqxmd.com/read/27846884/future-perspectives-in-melanoma-research-meeting-report-from-the-melanoma-bridge-napoli-december-1st-4th-2015
#15
Paolo A Ascierto, Sanjiv Agarwala, Gerardo Botti, Alessandra Cesano, Gennaro Ciliberto, Michael A Davies, Sandra Demaria, Reinhard Dummer, Alexander M Eggermont, Soldano Ferrone, Yang Xin Fu, Thomas F Gajewski, Claus Garbe, Veronica Huber, Samir Khleif, Michael Krauthammer, Roger S Lo, Giuseppe Masucci, Giuseppe Palmieri, Michael Postow, Igor Puzanov, Ann Silk, Stefani Spranger, David F Stroncek, Ahmad Tarhini, Janis M Taube, Alessandro Testori, Ena Wang, Jennifer A Wargo, Cassian Yee, Hassane Zarour, Laurence Zitvogel, Bernard A Fox, Nicola Mozzillo, Francesco M Marincola, Magdalena Thurin
The sixth "Melanoma Bridge Meeting" took place in Naples, Italy, December 1st-4th, 2015. The four sessions at this meeting were focused on: (1) molecular and immune advances; (2) combination therapies; (3) news in immunotherapy; and 4) tumor microenvironment and biomarkers. Recent advances in tumor biology and immunology has led to the development of new targeted and immunotherapeutic agents that prolong progression-free survival (PFS) and overall survival (OS) of cancer patients. Immunotherapies in particular have emerged as highly successful approaches to treat patients with cancer including melanoma, non-small cell lung cancer (NSCLC), renal cell carcinoma (RCC), bladder cancer, and Hodgkin's disease...
November 15, 2016: Journal of Translational Medicine
https://www.readbyqxmd.com/read/27819295/il-21-signaling-is-essential-for-optimal-host-resistance-against-mycobacterium-tuberculosis-infection
#16
Matthew G Booty, Palmira Barreira-Silva, Stephen M Carpenter, Cláudio Nunes-Alves, Miye K Jacques, Britni L Stowell, Pushpa Jayaraman, Gillian Beamer, Samuel M Behar
IL-21 is produced predominantly by activated CD4(+) T cells and has pleiotropic effects on immunity via the IL-21 receptor (IL-21R), a member of the common gamma chain (γc) cytokine receptor family. We show that IL-21 signaling plays a crucial role in T cell responses during Mycobacterium tuberculosis infection by augmenting CD8(+) T cell priming, promoting T cell accumulation in the lungs, and enhancing T cell cytokine production. In the absence of IL-21 signaling, more CD4(+) and CD8(+) T cells in chronically infected mice express the T cell inhibitory molecules PD-1 and TIM-3...
November 7, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27809352/t-bet-mediated-tim-3-expression-dampens-monocyte-function-during-chronic-hepatitis-c-virus-infection
#17
Wenjing Yi, Peixin Zhang, Yan Liang, Yun Zhou, Huanjun Shen, Chao Fan, Jonathan P Moorman, Zhi Q Yao, Zhansheng Jia, Ying Zhang
Hepatitis C virus (HCV) induces a high rate of chronic infection via dysregulation of host immunity. We have previously shown that T-cell immunoglobulin and mucin domain protein-3 (Tim-3) is up-regulated on monocyte/macrophages (M/Mφ) during chronic HCV infection; little is known, however, about the transcription factor that controls its expression in these cells. In this study, we investigated the role of transcription factor, T-box expressed in T cells (T-bet), in Tim-3 expression in M/Mφ in the setting of HCV infection...
November 3, 2016: Immunology
https://www.readbyqxmd.com/read/27807228/tim-1-promotes-hepatitis-c-virus-cell-attachment-and-infection
#18
Jing Wang, Luhua Qiao, Zhouhua Hou, Guangxiang Luo
: Human TIM and TAM family proteins were recently found to serve as phosphatidylserine (PS) receptors which promote infections by many different viruses, including dengue virus, West Nile virus, Ebola virus, Marburg virus, and Zika virus. In the present study, we provide substantial evidence demonstrating that TIM-1 is important for efficient infection by hepatitis C virus (HCV). The knockdown of TIM-1 expression significantly reduced HCV infection but not HCV RNA replication. Likewise, TIM-1 knockout in Huh-7...
January 15, 2017: Journal of Virology
https://www.readbyqxmd.com/read/27792920/t-cell-inflammation-profile-after-surgical-resection-may-predict-tumor-recurrence-in-hbv-related-hepatocellular-carcinoma
#19
Bin Song, Shoumei Zhen, Fanzhi Meng
The most effective treatment for HBV-related hepatocellular carcinoma (HCC) is surgical removal of the tumor in early stage patients. But many such patients will develop recurrent tumor within the first 24months, which is the major cause of death. To enable the prevention and earlier detection of recurrent HCC, we investigated the T cell responses that were potentially involved in HCC recurrence. We found that patients with recurrent HCC presented significantly lower frequencies of interferon gamma (IFNγ)-expressing Th1 cells and Tc1 cells, as well as significantly elevated Foxp3(+) Treg cells, in the peripheral blood and the resected primary tumor...
December 2016: International Immunopharmacology
https://www.readbyqxmd.com/read/27792886/tim-3-expression-on-immune-cells-and-roles-at-the-maternal-fetal-interface
#20
REVIEW
Xiao-Hui Hu, Mao-Xing Tang, Gil Mor, Ai-Hua Liao
Successful pregnancy relies on the accurate regulation of the maternal-fetal immune system. Without enough tolerance in the uterine microenvironment, the mother and the hemiallogeneic fetus could not peacefully coexist. T cell immunoglobulin and mucin domain (Tim)-3 is a molecule originally regarded as to be expressed on terminally differentiated IFN-γ expressing CD4(+) T cells (Th1). The engagement of Tim-3 with its ligand, galectin-9 (Gal-9) could induce the exhaustion or apoptosis of effector T cells, and thus might regulate the tolerance...
October 20, 2016: Journal of Reproductive Immunology
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