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https://www.readbyqxmd.com/read/28546465/quantitative-mass-spectrometry-analysis-of-pd-l1-protein-expression-n-glycosylation-and-expression-stoichiometry-with-pd-1-and-pd-l2-in-human-melanoma
#1
Carlos A Morales-Betanzos, Hyoungjoo Lee, Paula I Gonzalez-Ericsson, Justin M Balko, Douglas B Johnson, Lisa J Zimmerman, Daniel C Liebler
Quantitative assessment of key proteins that control the tumor-immune interface is one of the most formidable analytical challenges in immunotherapeutics. We developed a targeted mass spectrometry (MS) platform to quantify programmed cell death-1 (PD-1), programmed cell death 1 ligand 1 (PD-L1), and programmed cell death 1 ligand 2 (PD-L2) at fmol/microgram protein levels in formalin fixed, paraffin-embedded sections from 22 human melanomas. PD-L1 abundance ranged 50-fold, from approximately 0.03 to 1.5 fmol/microgram protein and the PRM data were largely concordant with total PD-L1-positive cell content, as analyzed by immunohistochemistry (IHC) with the E1L3N antibody...
May 25, 2017: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/28533488/tim-3-inhibits-low-density-lipoprotein-induced-atherogenic-responses-in-human-umbilical-vein-endothelial-cells
#2
Ming-Ke Qiu, Song-Cun Wang, Yong Tang, Chang Pan, Yang Wang, Shu-Qing Wang, Zhi-Wei Quan, Jing-Min Ou
Endothelial injury and dysfunction followed by endothelial activation and inflammatory cell recruitment are factors contributing to the initiation and progression of atherosclerosis. Oxidized low-density lipoprotein (ox-LDL) promotes inflammation during atherogenesis and lipid deposition in the arterial wall. We observed that stimulation of human umbilical vein endothelial cells (HUVECs) with ox-LDL activated pro-inflammatory cytokine production and apoptosis, inhibited cell migration, and upregulated T-cell immunoglobulin and mucin domain 3 (Tim-3) expression...
May 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28515387/functional-polymorphisms-affecting-th1-differentiation-are-associated-with-the-severity-of-autoimmune-thyroid-diseases
#3
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/28482851/checkpoint-inhibitors-in-hematological-malignancies
#4
REVIEW
Chi Young Ok, Ken H Young
Inhibitory molecules such as PD-1, CTLA-4, LAG-3, or TIM-3 play a role to keep a balance in immune function. However, many cancers exploit such molecules to escape immune surveillance. Accumulating data support that their functions are dysregulated in lymphoid neoplasms, including plasma cell myeloma, myelodysplastic syndrome, and acute myeloid leukemia. In lymphoid neoplasms, aberrations in 9p24.1 (PD-L1, PD-L2, and JAK2 locus), latent Epstein-Barr virus infection, PD-L1 3'-untranslated region disruption, and constitutive JAK-STAT pathway are known mechanisms to induce PD-L1 expression in lymphoma cells...
May 8, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28475007/tim-3-plays-a-more-important-role-than-pd-1-in-the-functional-impairments-of-cytotoxic-t-cells-of-malignant-schwannomas
#5
Zhao Li, Xiaobing Liu, Rongbin Guo, Pengfei Wang
Cancer immunotherapy using cytotoxic T cells demonstrates dramatic survival benefits in lymphomas, but its efficacy in solid tumors is limited. Here, we investigated the possibility of using cytotoxic T cells to treat malignant Schwannoma, a rare but aggressive nerve sheath tumor, by examining the native T-cell immunity in the host. We found that compared to CD8(+) T cells from healthy controls or benign Schwannoma patients, the CD8(+) T cells from malignant Schwannoma patients were present at normal frequencies but were substantially enriched with PD-1(-)TIM-3(+) and PD-1(+)TIM-3(+) cells...
May 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28466780/tim-3-expressing-macrophages-are-functionally-suppressed-and-expanded-in-oral-squamous-cell-carcinoma-due-to-virus-induced-gal-9-expression
#6
Jianfeng Dong, Lijun Cheng, Minchao Zhao, Xiangfeng Pan, Zhiqiang Feng, Dawei Wang
Oropharyngeal head and neck squamous cell carcinoma is a common malignant tumor in the oral cavity. High-risk human papillomavirus 16 infection is a major cause of oropharyngeal head and neck squamous cell carcinoma development. Strong antitumor immune responses, especially CD8(+) T cell responses, are thought to be essential to effective cancer treatment and are associated with better prognosis in oropharyngeal head and neck squamous cell carcinoma. In this study, we examined the role of the Tim-3/Gal-9 pathway in oropharyngeal head and neck squamous cell carcinoma patients...
May 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28441784/tim-3-up-regulation-in-patients-with-gastric-cancer-and-peptic-ulcer-disease
#7
Mahdieh aghavi-Alhosseini, Mohsen Tehrani, Abolghasem Ajami, Alireza Rafiei, Tarang Taghvaei, Laleh Vahedi-Larijani, Hadi Hossein-Nataj, Hossein Asgarian-Omran
Background: T-cell immunoglobulin and mucin domain protein-3 (Tim-3), an inhibitory immunoregulatory receptor, has been recently implicated in tumor biology and tumor-associated immune suppression. In the present study, expression of Tim-3 was evaluated in gastric cancer (GC) and peptic ulcer disease (PUD) at both mRNA and protein levels. Methods: A total of 133 gastric tissue biopsies, comprising 43 from GC cases, 48 from PUD and 42 from non-ulcer dyspepsia (NUD) serving as controls were collected. Additionally, non-neoplastic adjacent tissue biopsies were also obtained from 6 patients with GC...
March 1, 2017: Asian Pacific Journal of Cancer Prevention: APJCP
https://www.readbyqxmd.com/read/28440449/preoperative-tim%C3%A2-3-expression-on-peripheral-nk-cells-is-correlated-with-pathologic-tnm-staging-in-colorectal-cancer
#8
Yang Wang, Jintang Sun, Wenjuan Gao, Bingfeng Song, Qianqian Shao, Lei Zhao, Yun Zhang, Qingjie Wang, Yun Zhang, Xun Qu
Previous research has indicated that T cell immunoglobulin and mucin domain 3 (Tim-3) serves an important regulatory role in lymphocytes and in several cancers. However, the association between Tim‑3 expression on various lymphocyte subsets and human colorectal cancer (CRC) has not been elucidated. The present study aimed to characterize Tim‑3 expression on peripheral lymphocytes, including cluster of differentiation CD3+CD56‑ T cells, CD3‑CD56+ natural killer (NK) cells and CD3+CD56+ natural killer T (NKT) cells, in patients with CRC...
June 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28430664/identification-of-a-novel-pd-l1-positive-solid-tumor-transplantable-in-hla-a-0201-drb1-0101-transgenic-mice
#9
Laurie Rangan, Jeanne Galaine, Romain Boidot, Mohamad Hamieh, Magalie Dosset, Julie Francoual, Laurent Beziaud, Jean-René Pallandre, Elodie Lauret Marie Joseph, Afag Asgarova, Christophe Borg, Talal Al Saati, Yann Godet, Jean Baptiste Latouche, Séverine Valmary-Degano, Olivier Adotévi
HLA-A*0201/DRB1*0101 transgenic mice (A2/DR1 mice) have been developed to study the immunogenicity of tumor antigen-derived T cell epitopes. To extend the use and application of this mouse model in the field of antitumor immunotherapy, we described a tumor cell line generated from a naturally occurring tumor in A2/DR1 mouse named SARC-L1. Histological and genes signature analysis supported the sarcoma origin of this cell line. While SARC-L1 tumor cells lack HLA-DRB1*0101 expression, a very low expression of HLA-A*0201 molecules was found on these cells...
April 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28423678/influence-of-ipilimumab-on-expanded-tumour-derived-t-cells-from-patients-with-metastatic-melanoma
#10
Jon Bjoern, Rikke Lyngaa, Rikke Andersen, Lisbet Hölmich Rosenkrantz, Sine Reker Hadrup, Marco Donia, Inge Marie Svane
INTRODUCTION: Tumour infiltrating lymphocyte (TIL) based adoptive cell therapy (ACT) is a promising treatment for patients with advanced melanoma. Retrospective studies suggested an association between previous treatment with anti-CTLA-4 antibodies and long term survival after subsequent ACT. Thus, we hypothesized that treatment with anti-CTLA-4 antibodies can induce favourable changes to be detected in TILs. RESULTS: Expanded T cells from Ipilimumab treated patients had a higher proportion of cells expressing CD27, intracellular CTLA-4, TIM-3 and LAG-3...
April 18, 2017: Oncotarget
https://www.readbyqxmd.com/read/28423646/tim-3-is-a-potential-prognostic-marker-for-patients-with-solid-tumors-a-systematic-review-and-meta-analysis
#11
Yang Zhang, Pengcheng Cai, Tao Liang, Lin Wang, Lihua Hu
Accumulated studies have demonstrated the important role of T cell immunoglobulin- and mucin-domain-containing molecule-3 (TIM-3) in various solid tumors and indicated its correlation with patients' survival. To further verify the prognostic significance of TIM-3 in cancer patients and its correlation with tumor, we performed this meta-analysis including seven studies searched from PubMed, Web of Science, and Embase till July 2016. A total of 869 patients were used to analyze the association between TIM-3 expression and patients' overall survival (OS)...
May 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28423034/elevated-frequencies-of-cd8-t-cells-expressing-pd-1-ctla-4-and-tim-3-within-tumour-from-perineural-squamous-cell-carcinoma-patients
#12
Richard Linedale, Campbell Schmidt, Brigid T King, Annabelle G Ganko, Fiona Simpson, Benedict J Panizza, Graham R Leggatt
Perineural spread of tumour cells along cranial nerves is a severe complication of primary cutaneous squamous cell carcinomas of the head and neck region. While surgical excision of the tumour is the treatment of choice, removal of all the tumour is often complicated by the neural location and recurrence is frequent. Non-invasive immune treatments such as checkpoint inhibitor blockade may be useful in this set of tumours although little is understood about the immune response to perineural spread of squamous cell carcinomas...
2017: PloS One
https://www.readbyqxmd.com/read/28416578/withdrawn-quantitative-mass-spectrometry-analysis-of-pd-l1-protein-expression-n-glycosylation-and-expression-stoichiometry-with-pd-1-and-pd-l2-in-human-melanoma
#13
Carlos A Morales-Betanzos, Hyoungjoo Lee, Paula I Gonzalez-Ericsson, Justin M Balko, Douglas B Johnson, Lisa J Zimmerman, Daniel C Liebler
This article has been withdrawn by the authors. We discovered an error after this manuscript was published as a Paper in Press. Specifically, we learned that the structures of glycans presented for the PD-L1 peptide were drawn and labeled incorrectly. We wish to withdraw this article and submit a corrected version for review.
April 17, 2017: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/28408386/increased-pd-1-and-tim-3-tils-during-cetuximab-therapy-inversely-correlate-with-response-in-head-and-neck-cancer-patients
#14
Hyun-Bae Jie, Raghvendra M Srivastava, Athanassios Argiris, Julie E Bauman, Lawrence P Kane, Robert L Ferris
Despite emerging appreciation for the important role of immune checkpoint receptors in regulating the effector functions of T cells, it is unknown whether their expression is involved in determining the clinical outcome in response to cetuximab therapy. We examined the expression patterns of immune checkpoint receptors (including PD-1, CTLA-4, and TIM-3) and cytolytic molecules (including granzyme B and perforin) of CD8(+) tumor-infiltrating lymphocytes (TIL) and compared them with those of peripheral blood T lymphocytes (PBL) in patients with head and neck cancer (HNSCC) during cetuximab therapy...
May 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28401366/resistance-to-immunotherapy-clouds-in-a-bright-sky
#15
REVIEW
Gérard Milano
Two major challenges persist for an optimal management of immunotherapy: i) identifying those patients who will benefit from this type of therapy, and ii) determining the biological, cellular and molecular mechanisms that trigger disease progression while on therapy. There is a consensual view in favor of standardizing practices currently used to measure programmed death ligand 1 (PD-L1) expression that relates to innate resistance. The tumor mutation landscape has been widely explored as a potential predictor of treatment efficacy...
April 12, 2017: Investigational New Drugs
https://www.readbyqxmd.com/read/28401068/modulation-of-tim-3-expression-by-antigen-dependent-and-independent-factors-on-t-cells-from-patients-with-chronic-hepatitis-b-virus-infection
#16
Jie Dong, Xiao-Fei Yang, Lin-Xu Wang, Xin Wei, An-Hui Wang, Chun-Qiu Hao, Huan-Jun Shen, Chang-Xing Huang, Ye Zhang, Jian-Qi Lian
T-cell immunoglobulin domain and mucin domain-containing molecule-3 (Tim-3) was up-regulated on viral specific T cells and contributed to T cells exhaustion during chronic hepatitis B virus (HBV) infection. However, modulation of Tim-3 expression was still not fully elucidated. To evaluate the potential viral and inflammatory factors involved in the inductor of Tim-3 expression on T cells, 76 patients with chronic HBV infection (including 40 chronic hepatitis B [CHB] and 36 asymptomatic HBV carriers [AsC]) and 40 of normal controls (NCs) were enrolled in this study...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/28393295/elevated-galectin-9-suppresses-th1-effector-function-and-induces-apoptosis-of-activated-cd4-t-cells-in-osteoarthritis
#17
Shufeng Yang, Jin Wang, Fengrong Chen, Guoyin Liu, Zhiqiang Weng, Jianmin Chen
T cell immunoglobulin and mucin domain 3 (Tim-3) is a critical regulatory molecule found on activated Th1 cells, exhausted CD8(+) T cells, and resting monocytes/macrophages. Galectin-9 (Gal-9) is an identified ligand for Tim-3. Interaction between Tim-3 and Gal-9 is thought to inhibit Th1 responses. The regulation and function of Tim-3 and Gal-9 in osteoarthritis (OA) have not been intensively investigated. We found that in peripheral blood, CD4(+) T cells, but not CD8(+) T cells or CD14(+) monocytes, from OA patients presented significantly elevated Tim-3 and Gal-9 expression compared to those from healthy controls (HC)...
April 10, 2017: Inflammation
https://www.readbyqxmd.com/read/28374110/htlv-1-infection-and-neuropathogenesis-in-the-context-of-rag1-%C3%AE-c-rag1-hu-and-blt-mice
#18
Rashida Ginwala, Breanna Caruso, Zafar K Khan, Ajinkya Pattekar, Glen M Chew, Michael J Corley, Ronak Loonawat, Steven Jacobson, Sreesha Sreedhar, Lishomwa C Ndhlovu, Pooja Jain
To date, the lack of a suitable small animal model has hindered our understanding of Human T-cell lymphotropic virus (HTLV)-1 chronic infection and associated neuropathogenesis defined as HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). The host immune response plays a critical role in the outcome of HTLV-1 infection, which could be better tested in the context of humanized (hu) mice. Thus, we employ here the Balb/c-Rag1(-/-)γc(-/-) or Rag1 as well as Bone marrow-Liver-Thymic (BLT) mouse models for engraftment of human CD34(+) hematopoietic stem cells...
April 4, 2017: Journal of Neuroimmune Pharmacology: the Official Journal of the Society on NeuroImmune Pharmacology
https://www.readbyqxmd.com/read/28373665/polyfunctional-natural-killer-cells-with-a-low-activation-profile-in-response-to-toll-like-receptor-3-activation-in-hiv-1-exposed-seronegative-subjects
#19
Josenilson F Lima, Luanda M S Oliveira, Nátalli Z Pereira, Alberto J S Duarte, Maria N Sato
Natural killer (NK) cells are the main mediator of the cytotoxic response in innate immunity and may be involved in resistance to HIV-1 infection in exposed seronegative (ESN) individuals. Toll-like receptor (TLR) signalling is crucial for NK cell activation. Here, we investigated the polyfunctional NK cell response to TLR3 activation in serodiscordant couples. ESN subjects showed increased IFN-γ and CD107a expression in both NK subsets, CD56(bright) and CD56(dim) cells, in response to stimulation with a TLR3 agonist, while expression was impaired in the HIV-1-infected partners...
April 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28362657/epigenetics-of-cd4-t-cells-in-autoimmune-diseases
#20
Zijun Wang, Christopher Chang, Qianjin Lu
PURPOSE OF REVIEW: Autoimmune disorders are a group of overactive symptoms because of abnormal immune responses. Progress of novel mechanisms for autoimmune diseases has been restrained by incomplete understanding of immune disturbance. Recent advances in autoimmune diseases have been well documented by epigenetic alterations (DNA methylation, histone modification, and microRNAs), which alter the transcription activity of genes that are involved in autoimmune responses. RECENT FINDINGS: Multiple environmental factors (trichloroethylene, breast milk, and vitamin C) initiate aberrant epigenetic modifications in CD4 T cells, leading to a list of transcriptional deregulations in several genes (Ifng, Cd70, Tnf, Dnmt3a, and Foxp3) that determine T-cell identity...
March 30, 2017: Current Opinion in Rheumatology
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