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https://www.readbyqxmd.com/read/28935468/function-and-regulation-of-lag3-on-cd4-cd25-t-cells-in-non-small-cell-lung-cancer
#1
Qin-Yun Ma, Da-Yu Huang, Hui-Jun Zhang, Shaohua Wang, Xiao-Feng Chen
LAG3 is a surface molecule found on a subset of immune cells. The precise function of LAG3 appears to be context-dependent. In this study, we investigated the effect of LAG3 on CD4(+)CD25(-) T cells from non-small cell lung cancer (NSCLC) patients. We found that in the peripheral blood mononuclear cells of NSCLC patients, LAG3 was significantly increased in CD4(+) T cells directly ex vivo and primarily in the CD4(+)CD25(-) fraction, which was regulated by prolonged TCR stimulation and the presence of IL-27...
September 18, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28921877/analysis-of-infantile-fibrosarcoma-reveals-extensive-t-cell-responses-within-tumors-implications-for-immunotherapy
#2
Hua Zhu, Song Gu, Minzhi Yin, Min Shi, Chao Xin, Jianmin Zhu, Jing Wang, Siqi Huang, Chenjie Xie, Jing Ma, Ci Pan, Jingyan Tang, Min Xu, Xue-Feng Bai
BACKGROUND: Infantile fibrosarcoma (IFS) is a rare pediatric malignancy with relatively good prognosis, but the risk of progression or recurrence after therapy exists. To understand the immune microenvironment of IFS and determine if immunotherapy is a potential treatment, we analyzed T-cell responses in IFS tumors. PROCEDURE: IFS tumors were analyzed by immunohistochemistry and multicolor flow cytometry to characterize immune cell infiltration and function. Tumor infiltrating lymphocytes (TILs) were expanded in vitro and evaluated for recognition of autologous tumor cells...
September 17, 2017: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/28921767/expansion-of-cd4-phenotype-among-cd160-receptor-expressing-lymphocytes-in-murine-pregnancy
#3
Matyas Meggyes, Laszlo Szereday, Pal Jakso, Barbara Bogar, Agnes Bogdan, Jasper Nörenberg, Eva Miko, Aliz Barakonyi
PROBLEM: CD160, a cell surface co-receptor, is capable of up- or downregulating cell proliferation, cytotoxicity or cytokine production on lymphocytes. Our aim was to investigate CD160(+) lymphocytes in the periphery and at the maternal-foetal interface during murine pregnancy. METHOD OF STUDY: CD4(+) , CD8(+) and gamma/delta T-cell phenotype, TIM3 co-expression and cytotoxic activity of CD160(+) lymphocytes of pregnant BALB/c mice were analysed by flow cytometry...
September 16, 2017: American Journal of Reproductive Immunology: AJRI
https://www.readbyqxmd.com/read/28833046/ahr-activation-increases-il-2-production-by-alloresponding-cd4-t-cells-initiating-the-differentiation-of-mucosal-homing-tim3-lag3-tr1-cells
#4
Allison K Ehrlich, Jamie M Pennington, Susan Tilton, Xisheng Wang, Nikki B Marshall, Diana Rohlman, Castle Funatake, Sumit Punj, Edmond O'Donnell, Zhen Yu, Siva K Kolluri, Nancy I Kerkvliet
Activation of the aryl hydrocarbon receptor (AhR) by immunosuppressive ligands promotes the development of regulatory T (Treg) cells. Although AhR-induced Foxp3(+) Treg cells have been well studied, much less is known about the development and fate of AhR-induced Type 1 Treg (AhR-Tr1) cells. In the current study, we identified the unique transcriptional and functional changes in murine CD4(+) T cells that accompany the differentiation of AhR-Tr1 cells during the CD4(+) T-cell-dependent phase of an allospecific cytotoxic T lymphocyte (allo-CTL) response...
August 23, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28827755/low-tim3-expression-indicates-poor-prognosis-of-metastatic-prostate-cancer-and-acts-as-an-independent-predictor-of-castration-resistant-status
#5
Junlong Wu, Guowen Lin, Yao Zhu, Hailiang Zhang, Guohai Shi, Yijun Shen, Yiping Zhu, Bo Dai, Dingwei Ye
T cell immunoglobulin 3 (TIM3) is a cell surface star molecule expressed on T cells, and also marks dysfunctional CD8(+) T cells in various kinds of cancers. However, there are few studies focusing on the expression of TIM3 in tumor cells. In our study, we recruited 139 patients with metastatic prostate cancer (mPCa) who received transurethral resection of the prostate (TURP) consecutively to examine whether TIM3 expression level is associated with overall survival (OS) in mPCa patients. Immunohistochemistry was performed to determine TIM3 expression in prostate cancer tissues and then patients were divided into two groups...
August 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28806299/the-dynamic-and-transient-immune-microenvironment-in-locally-advanced-esophageal-adenocarcinoma-post-chemoradiation
#6
Ronan J Kelly, Ali H Zaidi, Matthew A Smith, Ashten N Omstead, Juliann E Kosovec, Daisuke Matsui, Samantha A Martin, Christina DiCarlo, E Day Werts, Jan F Silverman, David H Wang, Blair A Jobe
OBJECTIVE: The aim of this study was to assess the impact of chemoradiation on the immune microenvironment to influence and optimally design future neoadjuvant clinical trials. SUMMARY BACKGROUND DATA: Programmed death (PD)-1 inhibitors in metastatic gastroesophageal cancer have demonstrated response rates of approximately 25% in programmed death ligand-1 (PD-L1+) tumors. Unfortunately, the majority of patients do not respond. Therefore, a rationale strategy of combining immunotherapeutic agents with chemoradiation in earlier stage esophageal cancer may prevent metastatic disease in patients...
August 10, 2017: Annals of Surgery
https://www.readbyqxmd.com/read/28756232/tim3-galectin-9-alleviates-the-inflammation-of-tao-patients-via-suppressing-akt-nf-kb-signaling-pathway
#7
Li-Hua Luo, Dong-Mei Li, Yan-Ling Wang, Kang Wang, Li-Xin Gao, Shuang Li, Ji-Gang Yang, Chun-Lin Li, Wei Feng, Hong Guo
Thyroid-associated ophthalmopathy (TAO) is an autoimmune disease. Studies showed that T helper 1 (Th1), Th2, and Th17 cells play important roles in the pathology of TAO. Tim-3 and its only known ligand Galectin-9 (Gal-9) is related to the suppression of Th1 and Th17 cytokine secretion. This study aims to investigate the role of Tim3/Gal-9 in the inflammatory response of TAO. In this study, the levels of Tim3, Gal-9, and cytokines of Th1 (TNF-α and IFN-γ), Th2 (IL-4), and Th17 (IL-17) cells were analyzed in the blood samples of TAO patients and healthy controls as well as in orbital fibroblasts...
September 30, 2017: Biochemical and Biophysical Research Communications
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
#8
Yuan Chen, Shao-An Xue, Shahriar Behboudi, Goran Hamid Mohammad, Stephen P Pereira, Emma Morris
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/28686578/culling-of-apcs-by-inflammatory-cell-death-pathways-restricts-tim3-and-pd-1-expression-and-promotes-the-survival-of-primed-cd8-t-cells
#9
Rajen Patel, Kwangsin Kim, Bojan Shutinoski, Kristina Wachholz, Lakshmi Krishnan, Subash Sad
We evaluated the impact of premature cell death of antigen-presenting cells (APCs) by Caspase-1- and RipK3-signaling pathways on CD8(+) T-cell priming during infection of mice with Salmonella typhimurium (ST). Our results indicate that Caspase1 and RipK3 synergize to rapidly eliminate infected APCs, which does not influence the initial activation of CD8(+) T cells. However, the maintenance of primed CD8(+) T cells was greatly compromised when both these pathways were disabled. Caspase-1- and RipK3-signaling did not influence NF-κB signaling in APCs, but synergized to promote processing of IL-1 and IL-18...
July 7, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28648905/antibodies-against-immune-checkpoint-molecules-restore-functions-of-tumor-infiltrating-t-cells-in-hepatocellular-carcinomas
#10
Guoying Zhou, Dave Sprengers, Patrick P C Boor, Michail Doukas, Hannah Schutz, Shanta Mancham, Alexander Pedroza-Gonzalez, Wojciech G Polak, Jeroen de Jonge, Marcia Gaspersz, Haidong Dong, Kris Thielemans, Qiuwei Pan, Jan N M IJzermans, Marco J Bruno, Jaap Kwekkeboom
BACKGROUND & AIMS: Ligand binding to inhibitory receptors on immune cells, such as programmed cell death 1 (PD-1) and cytotoxic T-lymphocyte associated protein 4 (CTLA4), downregulates the T-cell-mediated immune response (called immune checkpoints). Antibodies that block these receptors increase anti-tumor immunity in patients with melanoma, non-small cell lung cancer, and renal cell cancer. Tumor-infiltrating CD4(+) and CD8(+) T cells in patients with hepatocellular carcinoma (HCC) have been found to be functionally compromised...
June 22, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28624961/phenotypic-and-functional-characterization-of-t-cells-in-white-matter-lesions-of-multiple-sclerosis-patients
#11
Gijsbert P van Nierop, Marvin M van Luijn, Samira S Michels, Marie-Jose Melief, Malou Janssen, Anton W Langerak, Werner J D Ouwendijk, Rogier Q Hintzen, Georges M G M Verjans
T cells are considered pivotal in the pathology of multiple sclerosis (MS), but their function and antigen specificity are unknown. To unravel the role of T cells in MS pathology, we performed a comprehensive analysis on T cells recovered from paired blood, cerebrospinal fluid (CSF), normal-appearing white matter (NAWM) and white matter lesions (WML) from 27 MS patients with advanced disease shortly after death. The differentiation status of T cells in these compartments was determined by ex vivo flow cytometry and immunohistochemistry...
June 17, 2017: Acta Neuropathologica
https://www.readbyqxmd.com/read/28615061/synergistic-effect-of-il-12-and-il-18-induces-tim3-regulation-of-%C3%AE-%C3%AE-t-cell-function-and-decreases-the-risk-of-clinical-malaria-in-children-living-in-papua-new-guinea
#12
Louis Schofield, Lisa J Ioannidis, Stephan Karl, Leanne J Robinson, Qiao Y Tan, Daniel P Poole, Inoni Betuela, Danika L Hill, Peter M Siba, Diana S Hansen, Ivo Mueller, Emily M Eriksson
BACKGROUND: γδ T cells are important for both protective immunity and immunopathogenesis during malaria infection. However, the immunological processes determining beneficial or detrimental effects on disease outcome remain elusive. The aim of this study was to examine expression and regulatory effect of the inhibitory receptor T-cell immunoglobulin domain and mucin domain 3 (TIM3) on γδ T cells. While TIM3 expression and function on conventional αβ T cells have been clearly defined, the equivalent characterization on γδ T cells and associations with disease outcomes is limited...
June 15, 2017: BMC Medicine
https://www.readbyqxmd.com/read/28600190/understanding-the-checkpoint-blockade-in-lung-cancer-immunotherapy
#13
REVIEW
Maria Giovanna Dal Bello, Angela Alama, Simona Coco, Irene Vanni, Francesco Grossi
Immunotherapies have changed the treatment strategy of some types of tumor including melanoma and, more recently, non-small-cell lung cancer (NSCLC). Immune checkpoints are crucial for the maintenance of self-tolerance and it is known that some tumors use checkpoint systems to evade antitumor immune response. The treatment of advanced NSCLC by immune-checkpoint blockade targeting the programmed cell death protein-1 (PD1/PDL1) and cytotoxic T-lymphocyte antigen 4 (CTLA4) pathways has led to significant clinical benefit either as monotherapy or in combination therapy...
August 2017: Drug Discovery Today
https://www.readbyqxmd.com/read/28578092/construction-of-human-masp-2-ccp1-2sp-ccp2sp-sp-plasmid-dna-nanolipoplexes-and-the-effects-on-tuberculosis-in-bcg-infected-mice
#14
Qi Gao, Xinfang Dong, Yanping Luo, Guochao Zhang, Jinyu Shan, Qian Wang, Qi He, Lifeng Zhang, Jingqiu Wang, Bingdong Zhu, Xingming Ma
The lectin pathway, one of the complement cascade systems, provides the primary line of defense against invading pathogens. The serine protease of MASP-2 plays an essential role in complement activation of the lectin pathway. The C-terminal segment of MASP-2 is comprised of the CCP1-CCP2-SP domains, and is the crucial catalytic segment. However, what is the effect of CCP1-CCP2-SP domains in controlling chronic infection is unknown. In order to evaluate the potential impact of CCP1-CCP2-SP domains on tuberculosis, we constructed the human MASP-2 CCP1/2SP, CCP2SP and SP recombinant plasmids, and delivered these plasmids by DNA-DOTAP:cholesterol cationic nanolipoplexes to BCG-infected mice...
May 31, 2017: Microbial Pathogenesis
https://www.readbyqxmd.com/read/28515387/functional-polymorphisms-affecting-th1-differentiation-are-associated-with-the-severity-of-autoimmune-thyroid-diseases
#15
Naoya Inoue, Mikio Watanabe, Azusa Nakaguchi, Daishi Ueda, Hayaka Kawaguti, Yoh Hidaka, Yoshinori Iwatani
The prognosis for autoimmune thyroid diseases (AITDs), such as Hashimoto's disease (HD) and Graves' disease (GD), varies among patients. Interleukin (IL)-12 and IL-18 also induce Th1 differentiation, and SOCS1 (Suppressor of cytokine signaling 1) and TIM-3 (T cell immunoglobulin and mucin domain-3) are known to be negative regulators of Th1 cells. To clarify the association of functional polymorphisms in the IL12, IL12Rβ1, IL18, SOCS1 and TIM3 genes with the intractability and severity of autoimmune thyroid disease (AITD), we genotyped these polymorphisms in 151 GD patients, including 61 patients with intractable GD and 51 patients with GD in remission, in 140 HD patients, including 59 patients with severe HD and 55 patients with mild HD, and in 74 healthy controls...
May 16, 2017: Endocrine Journal
https://www.readbyqxmd.com/read/28447034/the-biomarkers-of-leukemia-stem-cells-in-acute-myeloid-leukemia
#16
REVIEW
Yahui Ding, Huier Gao, Quan Zhang
Acute myeloid leukemia (AML) is a heterogeneous disease characterized by morphology and chromosome aberrations with high mortality. Leukemia stem cells (LSCs) in AML played important roles in leukemia initiation, progression, and were considered to be the root of chemotherapeutic drug resistance and disease relapse. The identification and targeting LSCs depended on membrane markers like CD34, CD38, CD123, TIM3, CD25, CD32 and CD96. In addition, the transcription factors were also therapeutic targets in eradicating LSCs, such as histone deacetylases (HDACs), NF-κB, HIF-1α and β-catenin...
2017: Stem Cell Investigation
https://www.readbyqxmd.com/read/28351582/defining-an-inflamed-tumor-immunophenotype-in-recurrent-metastatic-squamous-cell-carcinoma-of-the-head-and-neck
#17
Glenn J Hanna, Hongye Liu, Robert E Jones, Alyssa F Bacay, Patrick H Lizotte, Elena V Ivanova, Mark A Bittinger, Megan E Cavanaugh, Amanda J Rode, Jonathan D Schoenfeld, Nicole G Chau, Robert I Haddad, Jochen H Lorch, Kwok-Kin Wong, Ravindra Uppaluri, Peter S Hammerman
OBJECTIVES: Immune checkpoint inhibitors have demonstrated clinical benefit in recurrent, metastatic (R/M) squamous cell carcinoma of the head and neck (SSCHN), but lacking are biomarkers that predict response. We sought to define an inflamed tumor immunophenotype in this R/M SCCHN population and correlate immune metrics with clinical parameters and survival. METHODS: Tumor samples were prospectively acquired from 34 patients to perform multiparametric flow cytometry and multidimensional clustering analysis integrated with next-generation sequencing data, clinical parameters and outcomes...
April 2017: Oral Oncology
https://www.readbyqxmd.com/read/28323897/hcv-coinfection-contributes-to-hiv-pathogenesis-by-increasing-immune-exhaustion-in-cd8-t-cells
#18
Norma Rallón, Marcial García, Javier García-Samaniego, Noelia Rodríguez, Alfonso Cabello, Clara Restrepo, Beatriz Álvarez, Rosa García, Miguel Górgolas, José M Benito
BACKGROUND: There are several contributors to HIV-pathogenesis or insufficient control of the infection. However, whether HIV/HCV-coinfected population exhibits worst evolution of HIV-pathogenesis remains unclear. Recently, some markers of immune exhaustion have been proposed as preferentially upregulated on T-cells during HIV-infection. Herein, we have analyzed T-cell exhaustion together with several other contributors to HIV-pathogenesis that could be affected by HCV-coinfection. PATIENTS AND METHODS: Ninety-six patients with chronic HIV-infection (60 HIV-monoinfected and 36 HIV/HCV-coinfected), and 20 healthy controls were included in the study...
2017: PloS One
https://www.readbyqxmd.com/read/28267900/augmentation-of-hepatitis-c-virus-specific-immunity-and-sustained-virologic-response
#19
S Shrivastava, E Wilson, B Poonia, L Tang, A Osinusi, A Kohli, S Kottilil
Treatment for chronic hepatitis C virus (HCV) infection has rapidly evolved into interferon-free directly acting antiviral regimens (DAA) that result in high sustained virologic response. DAAs primarily work by suppressing HCV replication and rely less on the immune system than interferon-based therapies. However, it is unclear whether the immune system recovers with suppression of HCV replication and contributes to HCV clearance with DAA therapy. We previously demonstrated HCV clearance is associated with increased HCV-specific immunity in CHCV-GT-1-infected patients during treatment with sofosbuvir (SOF)+ribavirin (RBV)...
March 7, 2017: Journal of Viral Hepatitis
https://www.readbyqxmd.com/read/28257599/immunosuppressive-drugs-affect-interferon-ifn-%C3%AE-and-programmed-cell-death-1-pd-1-kinetics-in-patients-with-newly-diagnosed-autoimmune-hepatitis
#20
C R Grant, B S Holder, R Liberal, M A Heneghan, Y Ma, G Mieli-Vergani, D Vergani, M S Longhi
Autoimmune hepatitis (AIH) is characterized by overwhelming effector immune responses associated with defective regulatory T cells (Tregs ). Several lines of evidence indicate CD4 as the main effectors involved in autoimmune liver damage. Herein we investigate the in-vitro effects of prednisolone, 6-mercaptopurine, cyclosporin, tacrolimus, mycophenolic acid (MPA) and rapamycin, immunosuppressive drugs (ISDs) used in AIH treatment, on the expression of proinflammatory cytokines, co-inhibitory molecules and ability to proliferate of CD4(+) CD25(-) cells, isolated from the peripheral blood of treatment-naive patients with AIH...
July 2017: Clinical and Experimental Immunology
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