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https://www.readbyqxmd.com/read/29213216/tumor-infiltrating-cd4-t-cells-in-patients-with-gastric-cancer
#1
Long Yuan, Benling Xu, Peng Yuan, Jinxue Zhou, Peng Qin, Lu Han, Guangyu Chen, Zhenlei Wang, Zengci Run, Peng Zhao, Quanli Gao
Background: T lymphocytes play an indispensably important role in clearing virus and tumor antigen. There is little knowledge about impacts of inhibitory molecules with cytokine on tumor-infiltrating CD4+ T-cells in the presence of gastric cancer (GC). This study investigated the distribution of tumor-infiltrating T-cells subset and the differentiation as well as inhibitory phenotype of T-cells from blood and tissues of GC patients. Materials and methods: Patients with GC diagnosed on the basis of pre-operative staging and laparotomy findings were approached for enrollment between 2014 and 2015 at the Affiliated Cancer Hospital of Zhengzhou University, China...
2017: Cancer Cell International
https://www.readbyqxmd.com/read/29211042/newly-emerging-immune-checkpoints-promises-for-future-cancer-therapy
#2
REVIEW
Robert J Torphy, Richard D Schulick, Yuwen Zhu
Cancer immunotherapy has been a great breakthrough, with immune checkpoint inhibitors leading the way. Despite the clinical effectiveness of certain immune checkpoint inhibitors, the overall response rate remains low, and the effectiveness of immunotherapies for many tumors has been disappointing. There is substantial interest in looking for additional immune checkpoint molecules that may act as therapeutic targets for cancer. Recent advances during the last decade have identified several novel immune checkpoint targets, including lymphocyte activation gene-3 (LAG-3), B and T lymphocyte attenuator (BTLA), programmed death-1 homolog (PD-1H), T-cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domain (TIM-3)/carcinoembryonic antigen cell adhesion molecule 1 (CEACAM1), and the poliovirus receptor (PVR)-like receptors...
December 6, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29197680/increased-co-expression-of-pd-1-tigit-and-klrg-1-on-tumor-reactive-cd8-t-cells-during-relapse-after-allo-sct
#3
Tim J A Hutten, Wieger J Norde, Rob Woestenenk, Ruo Chen Wang, Frans Maas, Michel Kester, J H Frederik Falkenburg, Sofia Berglund, Leo Luznik, Joop H Jansen, Nicolaas Schaap, Harry Dolstra, Willemijn Hobo
Allogeneic stem cell transplantation (allo-SCT) can be a curative treatment for patients with a hematological malignancy due to allo-reactive T cell responses recognizing minor histocompatibility antigens (MiHA). Yet, tumor immune escape mechanisms can cause failure of T cell immunity, leading to relapse. Tumor cells display low expression of co-stimulatory molecules and can up-regulate co-inhibitory molecules that, upon ligation with their counter receptors on the tumor-reactive T cells, inhibit T cell functionality...
November 29, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/29197679/recipient-t-cell-exhaustion-and-successful-adoptive-transfer-of-haploidentical-natural-killer-cells
#4
Robin L Williams, Sarah Cooley, Veronika Bachanova, Bruce R Blazar, Daniel J Weisdorf, Jeffrey S Miller, Michael R Verneris
NK cells mediate surveillance for malignancy. In some chemotherapy refractory myeloid leukemia patients, adoptive transfer of NK cells from haploidentical donors can induce remission. We have previously shown that remission induction is linked to NK persistence at D+14, but the factors influencing NK cell persistence are unknown. To address this question, patient samples from a phase I trial of NCI IL-15 in whom either did or did not show NK cell expansion were compared to healthy donor controls. Prior to lymphodepleting chemotherapy, high absolute CD3+ count was predictive of patients who failed to expand their haplo-NK cell graft...
November 29, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/29194342/tim-3-regulates-tregs-ability-to-resolve-the-inflammation-and-proliferation-of-acute-lung-injury-by-modulating-macrophages-polarization
#5
Xiandong Liu, Sen Jiang, Qian Zhang, Shumin Xu, Xiaowei Bao, Wei Cao, Jianwen Bai, Lunxian Tang
We recently reported that CD4CD25 regulatory T cells (Tregs) contributed to the recovery of patients with acute lung injury (ALI) by upregulating T cell immunoglobulin and mucin-domain containing-3 (Tim-3). However, the molecular mechanism by which Tim-3 regulates Tregs' function in the resolution and fibroproliferation after ALI remains unknown. In this study, we adoptively transferred Tim-3Tregs or Tim-3Tregs into LPS-induced ALI mice model. Data demonstrated that Tim-3Tregs not only decreased indices of lung inflammation and injury but also mitigated lung fibrosis after ALI...
November 30, 2017: Shock
https://www.readbyqxmd.com/read/29179486/functional-expression-of-tim-3-on-blasts-and-clinical-impact-of-its-ligand-galectin-9-in-myelodysplastic-syndromes
#6
Toshio Asayama, Hideto Tamura, Mariko Ishibashi, Yasuko Kuribayashi-Hamada, Asaka Onodera-Kondo, Namiko Okuyama, Akiko Yamada, Masumi Shimizu, Keiichi Moriya, Hidemi Takahashi, Koiti Inokuchi
T-cell immunoglobulin mucin-3 (Tim-3), an inhibitory immune checkpoint receptor, is highly expressed on acute myeloid leukemia cells and its ligand galectin-9 is reported to drive leukemic progression by binding with Tim-3. However, it remains unclear whether the Tim-3-galectin-9 pathway is associated with the pathophysiology of myelodysplastic syndromes (MDS). Thus, we investigated the expression and function of Tim-3 and the clinical impact of its ligand galectin-9 in MDS. Tim-3 expression levels on MDS blasts by CD45/side-scatter or CD34/CD45 gating were increased as MDS progressed to the advanced stage...
October 24, 2017: Oncotarget
https://www.readbyqxmd.com/read/29174343/tim-3-expression-predicts-the-abnormal-innate-immune-status-and-poor-prognosis-of-glioma-patients
#7
Xueen Li, Bo Wang, Lintao Gu, Lifen Gao, Chunhong Ma, Xiaohong Liang, Xingang Li
Malignant glioma, the most common and devastating primary brain tumor, has serious effects on human health with high risk of recurrence and short survival periods. Recently, the exploitation of immunological mechanisms shed new lights for developing novel therapeutic strategies for glioma pathogenesis. Tim-3, a member of T cell immunoglobulin and mucin domain family, has been involved in multiple diseases, including tumor, by regulating the viability and function of immunocytes. In the present study, we detected Tim-3 expression on peripheral innate immunocytes from glioma patients and analyzed their correlation with clinical indices...
November 21, 2017: Clinica Chimica Acta; International Journal of Clinical Chemistry
https://www.readbyqxmd.com/read/29163783/abundant-expression-of-tim-3-lag-3-pd-1-and-pd-l1-as-immunotherapy-checkpoint-targets-in-effusions-of-mesothelioma-patients
#8
Elly Marcq, Jorrit De Waele, Jonas Van Audenaerde, Eva Lion, Eva Santermans, Niel Hens, Patrick Pauwels, Jan P van Meerbeeck, Evelien L J Smits
Malignant pleural mesothelioma (MPM) is an aggressive cancer with an increasing incidence, poor prognosis and limited effective treatment options. Hence, new treatment strategies are warranted which include immune checkpoint blockade approaches with encouraging preliminary data. Research on the immunological aspects of the easily accessible mesothelioma microenvironment could identify prognostic and/or predictive biomarkers and provide useful insights for developing effective immunotherapy. In this context, we investigated the immune cell composition of effusions (pleural and ascites fluids) from 11 different chemotherapy-treated MPM patients...
October 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/29163509/downregulated-il-21-response-and-t-follicular-helper-cell-exhaustion-correlate-with-compromised-cd8-t-cell-immunity-during-chronic-toxoplasmosis
#9
Magali M Moretto, SuJin Hwang, Imtiaz A Khan
CD8 T cells are important for maintaining the chronicity of Toxoplasma gondii infection. In a T. gondii encephalitis susceptible model, we recently demonstrated that CD4 T cells play an essential helper role in the maintenance of the effector response and CD8 T cell dysfunctionality was linked to CD4 T cell exhaustion. However, CD4 T cells are constituted of different subsets with various functions and the population(s) providing help to the CD8 T cells has not yet been determined. In the present study, T follicular helper cells (Tfh), which are known to be essential for B cell maturation and are one of the main sources of IL-21, were significantly increased during chronic toxoplasmosis...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29154820/cytotoxic-t-cell-responses-to-streptococcus-are-associated-with-improved-prognosis-of-oral-squamous-cell-carcinoma
#10
Jie Wang, Feng Sun, Xiaoyu Lin, Zaiye Li, Xiaohe Mao, Canhua Jiang
Several species of Streptococcus, such as S. salivarius, S. mitis, and S. anginosus, are found to extensively colonize the oral cavity and the upper respiratory tract, and have been shown to increase in patients with oral squamous cell carcinoma (OSCC). Accumulating evidence have revealed that commensal bacteria are involved in antitumor immunity via T cell-mediated mechanisms, but the role of Streptococcus enrichment in OSCC is yet unclear. In this study, we stimulated peripheral blood mononuclear cells from non-cancer controls (NCs) and OSCC patients with S...
November 14, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/29141799/the-4259a-c-polymorphism-of-tim-3-but-not-1637c-t-polymorphism-of-tim-1-is-associated-with-multiple-sclerosis-in-isfahan-population
#11
Masoumeh Pouladian, Mazdak Ganjalikhani-Hakemi, Fereshteh Alsahebfosul, Vida Homayouni, Sharifeh Khosravi, Masoud Etemadifar, Fariba Mazrouei, Rasoul Salehi
BACKGROUND: Multiple sclerosis (MS) is an inflammatory disease of the central nervous system (CNS) which initiated and mediated by autoreactive T helper1 cells directed against myelin antigens. One of T cell surface receptors is T cell immunoglobulin and mucin domain (TIM) family which its importance in immunology is recently discovered. These molecules have important immunological function by regulation of T effector cells. METHODS: In the present study, we analyzed the frequency of +4259A>C polymorphism in TIM-3 and -1637C>T polymorphism in TIM-1 gene in MS patients and healthy controls using restriction fragment length polymorphism-polymerase chain reaction (RFLP-PCR) method...
November 2017: Multiple Sclerosis and related Disorders
https://www.readbyqxmd.com/read/29141374/-association-of-pd-1-tim-3-and-trem-1-single-nucleotide-polymorphisms-with-pulmonary-tuberculosis-susceptibility
#12
F M Wang, X Zhang, L Lan, J M Ji, H B Tang, X J Yao, Y Jiang, J Qian, X G Xu, Q Li, P Yao, J H Li, Y P Shen
Objective: To investigate the association of programmed cell death 1(PD-1), T cell immunoglobulin mucin 3 (TIM-3) and triggering receptor expressed on myeloid cells-1 (TREM-1) genes polymorphisms with pulmonary tuberculosis susceptibility. Methods: In this case-control study, peripheral venous blood of 100 pulmonary tuberculosis patients (pulmonary tuberculosis group) in the Jintan People's Hospital of Changzhou and of community physical examination volunteers (health control group) was collected from Mar 2015 to Sep 2016...
November 14, 2017: Zhonghua Yi Xue za Zhi [Chinese medical journal]
https://www.readbyqxmd.com/read/29135922/targeting-immune-cell-checkpoints-during-sepsis
#13
REVIEW
Naeem K Patil, Yin Guo, Liming Luan, Edward R Sherwood
Immunosuppression is increasingly being recognized as one of the causes of increased morbidity and mortality during sepsis. Both innate and adaptive immune system dysfunction have been shown to cause an impaired ability to eradicate the primary infection and also lead to frequent occurrence of secondary opportunistic infections. Pre-clinical and clinical studies have shown that inhibitory immune checkpoint molecules, including programmed death-1 (PD-1), programmed death ligand-1 (PD-L1), cytotoxic T lymphocyte antigen-4 (CTLA-4), T cell membrane protein-3 (TIM-3), Lymphocyte activation-gene-3 (LAG-3) and 2B4, are upregulated during the course of sepsis...
November 14, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29127350/memory-regulatory-t-cells-increase-only-in-inflammatory-phase-of-chronic-hepatitis-b-infection-and-related-to-galectin-9-tim-3-interaction
#14
Ching-Chih Hu, Wen-Juei Jeng, Yi-Cheng Chen, Jian-He Fang, Chien-Hao Huang, Wei Teng, Yi-Chung Hsieh, Yung-Chang Lin, Rong-Nan Chien, I-Shyan Sheen, Chun-Yen Lin
CD4(+)Foxp3(+) regulatory T cells (Tregs) are the main immune suppressors with subpopulation of inflamed-tissue related memory Tregs (mTregs) and non-related resting Treg (rTregs). Previously, Treg was proposed to be the cause of chronicity of hepatitis B virus (HBV) infection but with controversies. We then investigated the role of mTregs in distinct immune phases of chronic HBV infection, especially the non-inflammatory versus inflammatory phases. It was found mTregs but not rTregs increased only in the inflammatory phase and correlated with serum alanine aminotransferase (ALT) level...
November 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29127145/tim-3-engagement-promotes-effector-memory-t-cell-differentiation-of-human-antigen-specific-cd8-t-cells-by-activating-mtorc1
#15
Nina Chi Sabins, Olesya Chornoguz, Karen Leander, Fred Kaplan, Richard Carter, Michelle Kinder, Kurtis Bachman, Raluca Verona, Shixue Shen, Vipul Bhargava, Sandra Santulli-Marotto
T cell expression of TIM-3 following Ag encounter has been associated with a continuum of functional states ranging from effector memory T cells to exhaustion. We have designed an in vitro culture system to specifically address the impact of anti-TIM-3/TIM-3 engagement on human Ag-specific CD8 T cells during a normal response to Ag and found that anti-TIM-3 treatment enhances T cell function. In our in vitro T cell culture system, MART1-specific CD8 T cells were expanded from healthy donors using artificial APCs...
November 10, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29113224/t-cell-immunoglobulin-mucin-3-as-a-potential-inducer-of-the-epithelial-mesenchymal-transition-in-hepatocellular-carcinoma
#16
Huapeng Lin, Bin Yang, Mujian Teng
T-cell immunoglobulin mucin (TIM)-3 is an important member of the TIM gene family, which was thought to contribute to the progression of numerous types of cancer, including hepatocellular carcinoma (HCC); however, the mechanism underlying TIM-3 functions in HCC progression has not yet been extensively investigated. The present study aimed to investigate the function of TIM-3 in the metastasis of HCC and to determine whether the alteration of TIM-3 expression levels regulated the epithelial-mesenchymal transition (EMT) occurrence of HCC, using epithelial (E)-cadherin, neuronal (N)-cadherin, matrix metallopeptidase-9 (MMP-9), Twist 1, Slug, Snail, and Smad as EMT biomarkers...
November 2017: Oncology Letters
https://www.readbyqxmd.com/read/29107214/tim-3-enhances-brain-inflammation-by-promoting-m1-macrophage-polarization-following-intracerebral-hemorrhage-in-mice
#17
Anyong Yu, Xiaojun Zhang, Mo Li, Peng Ye, Haizhen Duan, Tianxi Zhang, Zhao Yang
Macrophage polarization contributes to brain inflammation following spontaneous intracerebral hemorrhage (ICH). T cell immunoglobulin and mucin domain-3 (Tim-3) has been identified to induce macrophage mediated inflammation following ICH. However, the regulation of Tim-3 on macrophage polarization following ICH has not been fully studied. In current experiment, we explored Tim-3 expression, macrophage polarization, brain water content and neurological function in WT and Tim-3(-)/(-) ICH mice. In addition, downstream transcriptional factor TRIF and IRF3 were also analyzed...
October 26, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/29099687/conjugated-bilirubin-upregulates-tim-3-expression-on-cd4-cd25-t-cells-anti-inflammatory-implications-for-hepatitis-a-virus-infection
#18
Jorge L Trujillo-Ochoa, Karla F Corral-Jara, Claudia L Charles-Niño, Arturo Panduro, Nora A Fierro
Bilirubin (BR), a metabolite with increased concentrations in plasma during viral hepatitis, has been recognized as a potential immune-modulator. We recently reported that conjugated BR (CB) augments regulatory T cell (Treg) suppressor activity during acute hepatitis A virus (HAV) infection. However, the mechanisms related to the effects of CB on Treg function in the course of hepatotropic viral diseases have not been elucidated. T cell immunoglobulin domain and mucin domain 3 (TIM-3), via its interactions with galectin-9 (GAL-9), is a receptor associated with enhanced Treg function...
November 3, 2017: Viral Immunology
https://www.readbyqxmd.com/read/29089040/veritable-antiviral-capacity-of-natural-killer-cells-in-chronic-hbv-infection-an-argument-for-an-earlier-anti-virus-treatment
#19
Xiaoyan Li, Liang Zhou, Lin Gu, Yurong Gu, Lubiao Chen, Yifan Lian, Yuehua Huang
BACKGROUND: There is limited information on innate immunity, especially natural killer (NK) cell function, in different chronic hepatitis B (CHB) stages. Therefore, we examined whether the clinical staging strategy accurately reflects veritable NK cell immunity. METHODS: A total of 237 eligible CHB patients and 22 healthy controls were enrolled in our study. Demographic and clinical data were collected, and the CHB phases (immune active-IA, immune tolerant phase-IT, inactive CHB-IC, and grey zone-GZ) were classified according to the latest American Association for the Study of Liver Disease guidelines...
October 31, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/29083087/upregulation-of-tim-3-expression-at-feto-maternal-interface-may-explain-embryo-survival-in-the-cbaxdba-2-model-of-abortion
#20
Fanfan Li, Jing Dang, Min Jiang, Mengzhou He, Meitao Yang, Jing Li, Haiyan Hao, Yuan Zhou, Wei Zuo, Yin Xie, Dongrui Deng
PROBLEM: To understand the mechanisms of action of Tim-3 at the maternal-fetal interface and explore how Tim-3 might be involved in the pathogenesis of abortion by constructing an in vitro trophoblast-lymphocyte system. METHODS OF STUDY: Female CBA/J × male DBA/2 matings were used as the abortion-prone model and CBA/J × male BALB/c matings as control. The expression of Tim-3 at the maternal-fetal interface and in the peripheral blood lymphocytes was measured by immunohistochemistry and Western blotting...
October 30, 2017: American Journal of Reproductive Immunology: AJRI
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