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Kamila Hladíková, Simona Partlová, Vladimír Koucký, Jan Bouček, Jean-Francois Fonteneau, Michal Zábrodský, Ruth Tachezy, Marek Grega, Radek Špíšek, Anna Fialová
BACKGROUND: Human papillomavirus (HPV) type 16 infection is one of the most important etiological agents of oropharyngeal squamous cell carcinoma. Patients with HPV-associated carcinomas of the head and neck were reported to have a better clinical outcome than patients with HPV-negative tumors. Because HPV16 E6 and E7 oncoproteins are highly immunogenic and constitutively expressed, HPV-specific T cell immunity may play the key role in improving the prognosis of these patients. METHODS: Tumor-derived T cells were expanded in high levels of IL-2 and stimulated with HPV16 E6/E7 peptides in the presence or absence of anti-PD-1 monoclonal antibody nivolumab and soluble Tim-3...
July 2018: Oral Oncology
Mohsen Abdolmaleki, Nazanin Mojtabavi, Mahdi Zavvar, Mohammad Vaezi, Farshid Noorbakhsh, Mohammad Hossein Nicknam
T cell exhaustion is an immunosuppressive mechanism which occurs in chronic viral infections, solid tumors and hematologic malignancies. Exhausted T cell has increased the expression of inhibitory receptors, and functional impairment. In this study, we investigated the expression from some of those inhibitory receptors being Programmed death 1 (PD-1), T cell immunoglobulin and mucin domain containing molecules 3 (TIM-3) and CD244 on T cells from Iranian acute myeloid leukemia (AML) patients. Peripheral blood samples were collected from Iranian newly diagnosed AML patients and flow cytometric analysis was accomplished for cell surface expression of PD-1, TIM-3, and CD244 on T lymphocytes...
June 2018: Iranian Journal of Allergy, Asthma, and Immunology
Norio Chihara, Asaf Madi, Takaaki Kondo, Huiyuan Zhang, Nandini Acharya, Meromit Singer, Jackson Nyman, Nemanja D Marjanovic, Monika S Kowalczyk, Chao Wang, Sema Kurtulus, Travis Law, Yasaman Etminan, James Nevin, Christopher D Buckley, Patrick R Burkett, Jason D Buenrostro, Orit Rozenblatt-Rosen, Ana C Anderson, Aviv Regev, Vijay K Kuchroo
The expression of co-inhibitory receptors, such as CTLA-4 and PD-1, on effector T cells is a key mechanism for ensuring immune homeostasis. Dysregulated expression of co-inhibitory receptors on CD4+ T cells promotes autoimmunity, whereas sustained overexpression on CD8+ T cells promotes T cell dysfunction or exhaustion, leading to impaired ability to clear chronic viral infections and diseases such as cancer1,2 . Here, using RNA and protein expression profiling at single-cell resolution in mouse cells, we identify a module of co-inhibitory receptors that includes not only several known co-inhibitory receptors (PD-1, TIM-3, LAG-3 and TIGIT) but also many new surface receptors...
June 13, 2018: Nature
Inna M Yasinska, Isabel Gonçalves Silva, Svetlana S Sakhnevych, Laura Ruegg, Rohanah Hussain, Giuliano Siligardi, Walter Fiedler, Jasmin Wellbrock, Marco Bardelli, Luca Varani, Ulrike Raap, Steffen Berger, Bernhard F Gibbs, Elizaveta Fasler-Kan, Vadim V Sumbayev
High mobility group box 1 (HMGB1) is a non-histone protein localised in the cell nucleus, where it interacts with DNA and promotes nuclear transcription events. HMGB1 levels are elevated during acute myeloid leukaemia (AML) progression followed by participation of this protein in triggering signalling events in target cells as a pro-inflammatory stimulus. This mechanism was hypothesised to be employed as a survival pathway by malignant blood cells and our aims were therefore to test this hypothesis experimentally...
2018: Oncoimmunology
Simone M Hayen, Henny G Otten, Saskia A Overbeek, André C Knulst, Johan Garssen, Linette E M Willemsen
Background: Non-digestible oligosaccharides promote colonization of beneficial gut bacteria and have direct immunomodulatory effects. Apical exposure of intestinal epithelial cells (IECs) to short-chain galacto-oligosaccharides and long-chain fructo-oligosaccharides (scGOS/lcFOS) in a transwell co-culture model enhanced the CpG-induced (TLR-9 ligand) T helper 1 (Th1) phenotype and regulatory IL-10 response of underlying peripheral mononuclear cells (PBMCs) of healthy donors. scGOS is derived from lactose and may pose risks in severe cow's milk allergic patients, and scFOS/lcFOS may be an alternative...
2018: Frontiers in Immunology
François Audenet, Adam M Farkas, Harry Anastos, Matthew D Galsky, Nina Bhardwaj, John P Sfakianos
PURPOSE: To explore the immune phenotype of peripheral blood mononuclear cells (PBMC) in patients with high-risk non-muscle invasive bladder cancer (NMIBC). METHODS: We prospectively collected blood samples from patients with high-risk NMIBC treated at our institution. PBMC were analyzed by flow cytometry to determine the frequency of T cells and NK cells and the expression of immunoregulatory molecules (Tim-3, TIGIT and PD-1). PBMC from healthy donors (HD) were included for comparison, and associations with response to BCG were investigated...
June 2, 2018: World Journal of Urology
Rehab Alnabhan, Ahmed Gaballa, Lisa-Mari Mörk, Jonas Mattsson, Michael Uhlin, Isabelle Magalhaes
BACKGROUND: The use of CD19 chimeric antigen receptor (CAR) T cells to treat B-cell malignancies has proven beneficial. Several groups use serum to produce CD19 CAR T cells. Today, ready-to-use serum-free media that require no addition of serum are commercially available. Therefore, it becomes important to evaluate the production of CD19 CAR T cells with and without the addition of serum. METHODS: T cells from buffy coats were cultured in AIM-V and TexMACS (TM) supplemented with 5% human serum (A5% and TM5%, respectively), and in TM without serum...
May 30, 2018: Cytotherapy
Hang Su, Huikang Xie, Chenyang Dai, Yijiu Ren, Yunlang She, Long Xu, Donglai Chen, Dong Xie, Liping Zhang, Gening Jiang, Chang Chen
OBJECTIVES: T-cell immunoglobulin and mucin-domain containing-3 (TIM-3) is a promising checkpoint. However, its features and prognostic value in lung adenocarcinoma remain undetermined. In this study, we aimed to characterize TIM-3 expression and its prognostic significance in patients with surgically resected lung adenocarcinoma. MATERIALS AND METHODS: Expression of TIM-3 and programmed cell death 1 (PD-1), and density of CD8+ tumor infiltrating lymphocytes (TILs) were evaluated by immunohistochemistry in resected lung adenocarcinoma...
July 2018: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
Xin Yu, Hongru Zhang, Linyan Yu, Meifang Liu, Zengyan Zuo, Qiuju Han, Jian Zhang, Zhigang Tian, Cai Zhang
The intestinal immune system is crucial for protection from pathogenic infection and maintenance of mucosal homeostasis. Here, we studied the intestinal immune microenvironment in a Salmonella typhimurium intestinal infection mouse model. Intestinal lamina propria macrophages are the main effector cells in innate resistance to intracellular microbial pathogens. We found that S. typhimurium infection augmented Tim-3 expression on intestinal lamina propria CD4+ T cells and enhanced galectin-9 expression on F4/80+ CD11b+ macrophages...
May 29, 2018: Infection and Immunity
Chaoyang Zhang, Feng Li, Jieyao Li, Yujie Xu, Liping Wang, Yi Zhang
BACKGROUND: Lung tumor is a major cause of cancer incidence and patient death. Chemotherapy is the primary therapy used to treat lung cancer. In addition to direct cytotoxic effect on tumor cells, chemotherapeutic drugs activate immune responses to exert antitumor function. Here, the effects of docetaxel on the inhibitory molecules, programmed cell death 1 (PD-1), cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), and T-cell immunoglobulin and mucin domain 3 (TIM-3) in T lymphocytes were explored in patients with lung adenocarcinoma...
May 5, 2018: Clinical Lung Cancer
Asmaa M Zahran, Mostafa F Mohammed Saleh, Mona M Sayed, Amal Rayan, Arwa Mohammed Ali, Helal Hetta
BACKGROUND: The bone marrow immunosuppressive microenvironment of AML patients sustains and modulates proliferation, survival and drug resistance of AML through deregulation of both innate and adaptive immune response. We aimed to investigate the level of Tregs, expression of Tim-3 on peripheral blood T cells, expression of CD200 in myeloid blasts in newly diagnosed AML patients with normal cytogenetics (AML-NC) and their prognostic impact. PATIENTS AND METHODS: This study included 40 patients with de novo AML-NC and 20 healthy controls...
May 15, 2018: Cancer Biomarkers: Section A of Disease Markers
Fengxiang Zhang, Jinsong Zhao, Dapeng Sun, Ning Wei
MiR-155 can inhibit the formation of atherosclerosis by interfering with the transformation of macrophages into foam cells that plays a critical role in the pathogenesis of atherosclerosis, but the precise mechanisms of miR-155 are still unknown. Herein, we observed that mRNA and protein expression levels of CEH were significantly upregulated in a dose- and time-dependent manner by transfected with miR-155 mimics in THP-1 macrophages. Further studies showed that overexpression of miR-155 can significantly inhibit foam cells formation, reduce intracellular CE accumulation and enhance the efflux of FC and cholesterol, result in a decrease of intracellular lipid accumulation; while this effect was significantly reversed by siCEH...
May 23, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Feifei Pu, Fengxia Chen, Zhicai Zhang, Jing Feng, Ping Xia
Aim: Variants of TIM-3/HAVCR2 3'UTR miRNA binding sites are significantly associated with cancer; however, roles in post-transcriptional regulation have not been elucidated. Methods: The regulatory and coding region single nucleotide polymorphisms (SNPs) of TIM-3/HAVCR2 were identified using an online database. Single nucleotide polymorphism Function Prediction was used to predict potential functional relevance of miRNA binding sites. Results: The analysis indicated rs9313439, rs4704846, rs3087616 and rs1036199 affect possible miRNA binding sites in TIM-3/HAVCR2 3'UTR...
June 2018: Future Science OA
G Joelsons, T Domenico, L F Gonçalves, R C Manfro
The aim of the present study was to evaluate messenger RNA expression in kidney allograft recipients. Forty-four kidney transplant recipients were evaluated up to three months after grafting. After transplantation, peripheral blood samples were drawn sequentially for real-time polymerase chain reaction analyses of perforin and TIM-3 genes. Biopsies were obtained to evaluate acute graft dysfunction and interpreted according to the Banff classification. Eight patients presented episodes of acute rejection. Recipients with rejection had significantly higher levels of TIM-3 mRNA transcripts compared to those without rejection (median gene expression 191...
2018: Brazilian Journal of Medical and Biological Research, Revista Brasileira de Pesquisas Médicas e Biológicas
Genevieve E Martin, Matthew Pace, John P Thornhill, Chansavath Phetsouphanh, Jodi Meyerowitz, Morgane Gossez, Helen Brown, Natalia Olejniczak, Julianne Lwanga, Gita Ramjee, Pontiano Kaleebu, Kholoud Porter, Christian B Willberg, Paul Klenerman, Nneka Nwokolo, Julie Fox, Sarah Fidler, John Frater
Efforts to both characterize and eradicate the HIV reservoir have been limited by the rarity of latently infected cells and the absence of a specific denoting biomarker. CD32a (FcγRIIa) has been proposed to be a marker for an enriched CD4 T cell HIV reservoir, but this finding remains controversial. Here, we explore the expression of CD32 on CD3+ CD4+ cells in participants from two primary HIV infection studies and identify at least three distinct phenotypes (CD32low , CD32+ CD14+ , and CD32high ). Of note, CD4 negative enrichment kits remove the majority of CD4+ CD32+ T cells, potentially skewing subsequent analyses if used...
2018: Frontiers in Immunology
Lydia Meder, Philipp Schuldt, Martin Thelen, Anna Schmitt, Felix Dietlein, Sebastian Klein, Sven Borchmann, Kerstin Wennhold, Ignacija Vlasic, Sebastian Oberbeck, Richard Riedel, Alexandra Florin, Kristina Golfmann, Hans Anton Schlößer, Margarete Odenthal, Reinhard Büttner, Juergen Wolf, Michael Hallek, Marco Herling, Michael von Bergwelt-Baildon, Hans Christian Reinhardt, Roland T Ullrich
Small cell lung cancer (SCLC) represents the most aggressive pulmonary neoplasm and is often diagnosed at late stage with limited survival, despite combined chemotherapies. We show in an autochthonous mouse model of SCLC that combined anti-VEGF/anti-PD-L1 targeted therapy synergistically improves treatment outcome compared to anti-PD-L1 and anti-VEGF monotherapy. Mice treated with anti-PD-L1 alone relapsed after 3 weeks and were associated with a tumor-associated PD-1/TIM-3 double positive exhausted T cell phenotype...
May 18, 2018: Cancer Research
Jung-Mao Hsu, Weiya Xia, Yi-Hsin Hsu, Li-Chuan Chan, Wen-Hsuan Yu, Jong-Ho Cha, Chun-Te Chen, Hsin-Wei Liao, Chu-Wei Kuo, Kay-Hooi Khoo, Jennifer L Hsu, Chia-Wei Li, Seung-Oe Lim, Shih-Shin Chang, Yi-Chun Chen, Guo-Xin Ren, Mien-Chie Hung
Enriched PD-L1 expression in cancer stem-like cells (CSCs) contributes to CSC immune evasion. However, the mechanisms underlying PD-L1 enrichment in CSCs remain unclear. Here, we demonstrate that epithelial-mesenchymal transition (EMT) enriches PD-L1 in CSCs by the EMT/β-catenin/STT3/PD-L1 signaling axis, in which EMT transcriptionally induces N-glycosyltransferase STT3 through β-catenin, and subsequent STT3-dependent PD-L1 N-glycosylation stabilizes and upregulates PD-L1. The axis is also utilized by the general cancer cell population, but it has much more profound effect on CSCs as EMT induces more STT3 in CSCs than in non-CSCs...
May 15, 2018: Nature Communications
H Shen, H Sheng, J J Lu, C Feng, M Yao, H Pan, L S Xu, J F Shen, Y Zheng, Y L Zhou
Objective: To explore the expression and distribution of programmed death receptor 1 (PD-1) and T-cell immunoglobulin mucin 3 (TIM-3) in breast cancer microenvironment and analyze the their correlation with the clinicopathological features. Methods: The specimens of tumor tissue and adjacent tissues from 30 patients with infiltrative breast cancer who were diagnosed as breast cancer from June 2016 to May 2017 in The First Hospital of Jiaxing were collected, and the specimen were divided into two parts along the center...
May 8, 2018: Zhonghua Yi Xue za Zhi [Chinese medical journal]
Rada Ellegård, Mohammad Khalid, Cecilia Svanberg, Hanna Holgersson, Ylva Thorén, Mirja Karolina Wittgren, Jorma Hinkula, Sofia Nyström, Esaki M Shankar, Marie Larsson
Dendritic cells (DCs), natural killer (NK) cells, and T cells play critical roles during primary HIV-1 exposure at the mucosa, where the viral particles become coated with complement fragments and mucosa-associated antibodies. The microenvironment together with subsequent interactions between these cells and HIV at the mucosal site of infection will determine the quality of immune response that ensues adaptive activation. Here, we investigated how complement and immunoglobulin opsonization influences the responses triggered in DCs and NK cells, how this affects their cross talk, and what T cell phenotypes are induced to expand following the interaction...
2018: Frontiers in Immunology
Fang Li, Na Li, Jiao Sang, Xiude Fan, Huan Deng, Xiaoge Zhang, Qunying Han, Yi Lv, Zhengwen Liu
Background and objective: Upregulated T-cell immunoglobulin and mucin domain containing molecule-3 (Tim-3) in hepatitis B virus (HBV)-specific CD8+ T-cells contributes to CD8+ T-cell exhaustion during chronic HBV infection. The membrane-bound Tim-3 can be cleaved from the cell surface by sheddase, yielding soluble Tim-3 (sTim-3). This study investigated serum sTim-3 levels in patients with chronic HBV infection of various liver diseases. Methods: Serum sTim-3 levels were quantitatively determined in 288 patients with chronic HBV infection of various liver diseases...
2018: Cancer Management and Research
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