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https://www.readbyqxmd.com/read/29648914/tx99-is-a-neutralizing-monoclonal-antibody-against-mouse-tigit
#1
Yuho Nakamura, Keisuke Naito, Yumi Yamashita-Kanemaru, Daisuke Komori, Rei Hirochika, Akira Shibuya, Kazuko Shibuya
T cell immunoglobulin and ITIM domains (TIGIT) is an inhibitory immunoreceptor expressed on NK cells, effector and memory T cells, and regulatory T cells (Tregs). The ligands for TIGIT are CD155 (PVR) and CD112 (PVRL2, nectin-2), which are broadly expressed on hematopoietic cells and nonhematopoietic cells. TIGIT negatively regulates antitumor responses, but promotes autoimmune reaction. Although neutralizing anti-human TIGIT mAbs are under clinical trials for cancers, how the blockade of TIGIT interaction with the ligands shows tumor immunity still remains unclear...
April 12, 2018: Monoclonal Antibodies in Immunodiagnosis and Immunotherapy
https://www.readbyqxmd.com/read/29619076/immunogenicity-of-a-fap2-peptide-mimotope-of-fusobacterium-nucleatum-and-its-potential-use-in-the-diagnosis-of-colorectal-cancer
#2
Leonardo A Guevarra, Andrea Claudine F Afable, Patricia Joyce O Belza, Karen Joy S Dy, Scott Justin Q Lee, Teresa T Sy-Ortin, Pia Marie S P Albano
Background: The role of Fusobacterium nucleatum Fap2 protein in the development of colorectal cancer has recently been explained. Fap2, when bound to the human inhibitory receptor, TIGIT, inhibits the cytotoxic activity of natural killer (NK) cells against cancer cells, thus, allowing proliferation of the latter eventually leading to tumor growth. The aim of the study was to identify the immunogenicity of a peptide mimotope of the Fap2 protein and to determine the reactivity of colorectal cancer patients' sera against the mimotope...
2018: Infectious Agents and Cancer
https://www.readbyqxmd.com/read/29615995/htlv-1-alters-t-cells-for-viral-persistence-and-transmission
#3
REVIEW
Azusa Tanaka, Masao Matsuoka
Human T-cell leukemia virus type 1 (HTLV-1) was the first retrovirus to be discovered as a causative agent of adult T-cell leukemia-lymphoma (ATL) and chronic inflammatory diseases. Two viral factors, Tax and HTLV-1 bZIP factor (HBZ), are thought to be involved in the leukemogenesis of ATL. Tax expression is frequently lost due to DNA methylation in the promoter region, genetic changes to the tax gene, and deletion of the 5' long terminal repeat (LTR) in approximately half of all ATL cases. On the other hand, HBZ is expressed in all ATL cases...
2018: Frontiers in Microbiology
https://www.readbyqxmd.com/read/29544515/next-generation-of-immune-checkpoint-therapy-in-cancer-new-developments-and-challenges
#4
REVIEW
Julian A Marin-Acevedo, Bhagirathbhai Dholaria, Aixa E Soyano, Keith L Knutson, Saranya Chumsri, Yanyan Lou
Immune checkpoints consist of inhibitory and stimulatory pathways that maintain self-tolerance and assist with immune response. In cancer, immune checkpoint pathways are often activated to inhibit the nascent anti-tumor immune response. Immune checkpoint therapies act by blocking or stimulating these pathways and enhance the body's immunological activity against tumors. Cytotoxic T lymphocyte-associated molecule-4 (CTLA-4), programmed cell death receptor-1 (PD-1), and programmed cell death ligand-1(PD-L1) are the most widely studied and recognized inhibitory checkpoint pathways...
March 15, 2018: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/29512870/dw2008s-and-its-major-constituents-from-justicia-procumbens-exert-anti-asthmatic-effect-via-multitargeting-activity
#5
Jihyun Youm, Hyunyong Lee, Youngwoo Choi, Joobyoung Yoon
Our previous study revealed that the ethanolic extract of Justicia procumbens ameliorates ovalbumin-induced airway inflammation and airway hyper-responsiveness in a mouse model of asthma. However, the mechanism of action of the extract remains unknown. In this study, we prepared DW2008S, an optimized and standardized powder extracted from J. procumbens using anhydrous ethanol, and investigated its anti-asthmatic effect and mechanism of action. Our results showed that DW2008S contains two major ingredients, justicidin A (JA) and justicidin B (JB), which selectively inhibit T helper 2 (Th2) cell responses in concanavalin A-activated spleen cells and polarized Th2 cells...
March 7, 2018: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/29512851/tigit-expression-levels-on-cd4-t-cells-are-correlated-with-disease-severity-in-patients-with-psoriasis
#6
F F Wang, Y Wang, L Wang, T S Wang, Y P Bai
BACKGROUND: T-cell immunoglobulin and ITIM domain (TIGIT), a co-inhibitory receptor, suppresses CD4+ T-cell responses by triggering CD155. TIGIT shifts the balance of cytokines, including interferon (IFN)-γ, interleukin (IL)-10 and IL-17A, and affects the proliferation of CD4+ T cells. AIM: To investigate TIGIT expression and its effects on CD4+ T-cell function in psoriasis. METHODS: In total, 28 patients with psoriasis vulgaris PV and 14 healthy controls (HCs) were enrolled...
March 7, 2018: Clinical and Experimental Dermatology
https://www.readbyqxmd.com/read/29505821/early-reconstitution-of-nk-and-%C3%AE-%C3%AE-t-cells-and-its-implication-for-the-design-of-post-transplant-immunotherapy
#7
Moniek A de Witte, Dhifaf Sarhan, Zachary Davis, Martin Felices, Daniel A Vallera, Peter Hinderlie, Julie Curtsinger, Sarah Cooley, John Wagner, Jurgen Kuball, Jeffrey S Miller
Relapse is the most frequent cause of treatment failure after allogeneic hematopoietic stem cell transplantation (allo-HCT). NK cells and γδ T cells reconstitute early after allo-HCT, contribute to tumor immunosurveillance via MHC independent mechanisms and do not induce graft-versus-host disease (GVHD). Here we performed a quantitative and qualitative analysis of the NK and γδ T cell repertoire in healthy individuals, recipients of HLA-matched sibling or unrelated donor allo-HCT (MSD/MUD-HCT) and umbilical cord blood-HCT (UCB-HCT)...
March 2, 2018: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/29500245/functional-anti-tigit-antibodies-regulate-development-of-autoimmunity-and-antitumor-immunity
#8
Karen O Dixon, Michelle Schorer, James Nevin, Yassaman Etminan, Zohreh Amoozgar, Takaaki Kondo, Sema Kurtulus, Nasim Kassam, Raymond A Sobel, Dai Fukumura, Rakesh K Jain, Ana C Anderson, Vijay K Kuchroo, Nicole Joller
Coinhibitory receptors, such as CTLA-4 and PD-1, play a critical role in maintaining immune homeostasis by dampening T cell responses. Recently, they have gained attention as therapeutic targets in chronic disease settings where their dysregulated expression contributes to suppressed immune responses. The novel coinhibitory receptor TIGIT (T cell Ig and ITIM domain) has been shown to play an important role in modulating immune responses in the context of autoimmunity and cancer. However, the molecular mechanisms by which TIGIT modulates immune responses are still insufficiently understood...
March 2, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29403500/human-immunodeficiency-virus-type-1-elite-controllers-maintain-low-co-expression-of-inhibitory-receptors-on-cd4-t-cells
#9
Kajsa Noyan, Son Nguyen, Michael R Betts, Anders Sönnerborg, Marcus Buggert
Human immunodeficiency virus type-1 (HIV-1) elite controllers (ELCs) represent a unique population that control viral replication in the absence of antiretroviral therapy (cART). It is well established that expression of multiple inhibitory receptors on CD8+ T cells is associated with HIV-1 disease progression. However, whether reduced co-expression of inhibitory receptors on CD4+ T cells is linked to natural viral control and slow HIV-1 disease progression remains undefined. Here, we report on the expression pattern of numerous measurable inhibitory receptors, associated with T cell exhaustion (programmed cell death-1, CTLA-4, and TIGIT), on different CD4+ T cell memory populations in ELCs and HIV-infected subjects with or without long-term cART...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29368793/different-aberrant-expression-pattern-of-immune-checkpoint-receptors-in-patients-with-ptcl-and-nk-t-cl
#10
Ziwei Liao, Xuewen Lv, Sichu Liu, Zifan He, Shaohua Chen, Liang Wang, Wenyu Li, Yangqiu Li
AIM: To better understand the T-cell immunodeficiency status in patients with peripheral T-cell lymphomas (PTCLs) and NK/T-cell lymphomas (NK/T-CLs), the T-cell inhibitory receptors expression pattern was investigated. METHODS: The expression levels of programmed death 1 (PD-1), cytotoxic T lymphocyte-associated antigen 4 (CTLA-4), B/T lymphocyte attenuator (BTLA), lymphocyte-activation gene 3 (LAG-3), T-cell immunoglobulin-3 (TIM-3), T-cell immunoglobulin and ITIM domain (TIGIT) genes were detected in peripheral blood mononuclear cells (PBMCs) from patients and healthy volunteers by quantitative real-time-PCR, the correlation between different gene expression levels was analyzed...
January 25, 2018: Asia-Pacific Journal of Clinical Oncology
https://www.readbyqxmd.com/read/29359507/immune-checkpoint-inhibitors-in-cancer-therapy-a-focus-on-t-regulatory-cells
#11
REVIEW
Varun Sasidharan Nair, Eyad Elkord
Regulatory T cells (Tregs) play essential roles in immune homeostasis; however, their role in tumor microenvironment (TME) is not completely evident. Several studies reported that infiltration of Tregs into various tumor tissues promotes tumor progression by limiting antitumor immunity and supporting tumor immune evasion. Furthermore, in TME, Tregs include heterogeneous subsets of cells expressing different immunosuppressive molecules favoring tumor progression. For an effective cancer therapy, it is critical to understand the Treg heterogeneity and biology in the TME...
January 2018: Immunology and Cell Biology
https://www.readbyqxmd.com/read/29349889/t-cell-immunoglobulin-and-itim-domain-contributes-to-cd8-t-cell-immunosenescence
#12
Yangzi Song, Beibei Wang, Rui Song, Yu Hao, Di Wang, Yuxin Li, Yu Jiang, Ling Xu, Yaluan Ma, Hong Zheng, Yaxian Kong, Hui Zeng
Aging is associated with immune dysfunction, especially T-cell defects, which result in increased susceptibility to various diseases. Previous studies showed that T cells from aged mice express multiple inhibitory receptors, providing evidence of the relationship between T-cell exhaustion and T-cell senescence. In this study, we showed that T-cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif (ITIM) domain (TIGIT), a novel co-inhibitory receptor, was upregulated in CD8+ T cells of elderly adults...
April 2018: Aging Cell
https://www.readbyqxmd.com/read/29282307/cutting-edge-low-affinity-tcrs-support-regulatory-t-cell-function-in-autoimmunity
#13
Maran L Sprouse, Ivan Shevchenko, Marissa A Scavuzzo, Faith Joseph, Thomas Lee, Samuel Blum, Malgorzata Borowiak, Matthew L Bettini, Maria Bettini
Regulatory T cells (Tregs) use a distinct TCR repertoire and are more self-reactive compared with conventional T cells. However, the extent to which TCR affinity regulates the function of self-reactive Tregs is largely unknown. In this study, we used a two-TCR model to assess the role of TCR affinity in Treg function during autoimmunity. We observed that high- and low-affinity Tregs were recruited to the pancreas and contributed to protection from autoimmune diabetes. Interestingly, high-affinity cells preferentially upregulated the TCR-dependent Treg functional mediators IL-10, TIGIT, GITR, and CTLA4, whereas low-affinity cells displayed increased transcripts for Areg and Ebi3 , suggesting distinct functional profiles...
February 1, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29245183/increased-expression-and-modulated-regulatory-activity-of-coinhibitory-receptors-pd-1-tigit-and-tim-3-in-lymphocytes-from-patients-with-systemic-sclerosis
#14
Michelle Fleury, Anna C Belkina, Elizabeth A Proctor, Christopher Zammitti, Robert W Simms, Douglas A Lauffenburger, Jennifer E Snyder-Cappione, Robert Lafyatis, Hans Dooms
OBJECTIVE: Immune dysfunction is an important component of the disease process underlying systemic sclerosis (SSc), but the mechanisms contributing to altered immune cell function in SSc remain poorly defined. This study was undertaken to measure the expression and function of the coinhibitory receptors (co-IRs) programmed cell death 1 (PD-1), T cell immunoglobulin and ITIM domain (TIGIT), T cell immunoglobulin and mucin domain 3 (TIM-3), and lymphocyte activation gene 3 (LAG-3) in lymphocyte subsets from the peripheral blood of patients with SSc...
December 15, 2017: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/29217528/t-cells-expressing-checkpoint-receptor-tigit-are-enriched-in-follicular-lymphoma-tumors-and-characterized-by-reversible-suppression-of-t-cell-receptor-signaling
#15
Sarah E Josefsson, Kanutte Huse, Arne Kolstad, Klaus Beiske, Daniela Pende, Chloé B Steen, Else Marit Inderberg, Ole Christian Lingjærde, Bjørn Østenstad, Erlend B Smeland, Ronald Levy, Jonathan M Irish, June H Myklebust
Purpose: T cells infiltrating follicular lymphoma (FL) tumors are considered dysfunctional, yet the optimal target for immune checkpoint blockade is unknown. Characterizing coinhibitory receptor expression patterns and signaling responses in FL T-cell subsets might reveal new therapeutic targets. Experimental Design: Surface expression of 9 coinhibitory receptors governing T-cell function was characterized in T-cell subsets from FL lymph node tumors and from healthy donor tonsils and peripheral blood samples, using high-dimensional flow cytometry...
February 15, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29212853/emergence-of-high-avidity-melan-a-specific-clonotypes-as-a-reflection-of-anti-pd-1-clinical-efficacy
#16
Sylvain Simon, Virginie Vignard, Emilie Varey, Tiphaine Parrot, Anne-Chantal Knol, Amir Khammari, Nadine Gervois, Francois Lang, Brigitte Dreno, Nathalie Labarriere
Therapeutic strategies using anti-PD-1-blocking antibodies reported unparalleled effectiveness for melanoma immunotherapy, but deciphering immune responses modulated by anti-PD-1 treatment remains a crucial issue. Here, we analyzed the composition and functions of the large Melan-A-specific T-cell repertoire in the peripheral blood of 9 melanoma patients before and after 2 months of treatment with anti-PD-1. We observed amplification of Melan-A-specific Vß subfamilies undetectable before therapy (thereafter called emerging Vß subfamilies) in responding patients, with a predominant expansion in patients with a complete response...
December 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/29197680/increased-coexpression-of-pd-1-tigit-and-klrg-1-on-tumor-reactive-cd8-t-cells-during-relapse-after-allogeneic-stem-cell-transplantation
#17
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 hematologic malignancy due to alloreactive 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 costimulatory molecules and can up-regulate coinhibitory molecules that inhibit T cell functionality on ligation with their counter-receptors on the tumor-reactive T cells...
December 26, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/29147616/mrna-expression-levels-of-genes-involved-in-antitumor-immunity-identification-of-a-3-gene-signature-associated-with-prognosis-of-muscle-invasive-bladder-cancer
#18
Constance Le Goux, Sophie Vacher, Géraldine Pignot, Mathilde Sibony, Nicolas Barry Delongchamps, Benoit Terris, Eliane Piaggio, Marc Zerbib, Diane Damotte, Ivan Bieche
Immunotherapy for bladder cancer has given promising results. Here we aimed to evaluate the possible involvement and prognostic value of 33 genes involved in the immune response during bladder carcinogenesis. Expression levels were assessed by quantitative real-time RT-PCR in normal and tumor human bladder samples. Immunohistochemistry was performed to evaluate the protein expression of 2 genes and relation of the mRNA and protein levels was analyzed. Tumors were obtained from 154 patients (83 with muscle-invasive bladder cancer [MIBC] and 71 non-MIBC [NMIBC]) who underwent transurethral bladder resection or radical cystectomy between 2002 and 2006...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/29118008/ctla-4-a-moving-target-in-immunotherapy
#19
REVIEW
Behzad Rowshanravan, Neil Halliday, David M Sansom
CD28 and CTLA-4 are members of a family of immunoglobulin-related receptors that are responsible for various aspects of T-cell immune regulation. The family includes CD28, CTLA-4, and ICOS as well as other proteins, including PD-1, BTLA, and TIGIT. These receptors have both stimulatory (CD28, ICOS) and inhibitory roles (CTLA-4, PD-1, BTLA , and TIGIT) in T-cell function. Increasingly, these pathways are targeted as part of immune modulatory strategies to treat cancers, referred to generically as immune checkpoint blockade, and conversely to treat autoimmunity and CTLA-4 deficiency...
January 4, 2018: Blood
https://www.readbyqxmd.com/read/29115974/stat3-blocked-whole-cell-hepatoma-vaccine-induces-cellular-and-humoral-immune-response-against-hcc
#20
Qiuju Han, Yaqun Wang, Min Pang, Jian Zhang
BACKGROUND: Whole-cell tumor vaccines have shown much promise; however, only limited success has been achieved for the goal of eliciting robust tumor-specific T-cell responses. METHODS: Hepatocellular carcinoma (HCC) cells, H22 and Hepa1-6, were modified by blocking the STAT3 signaling pathway with a STAT3 decoy oligodeoxynucleotide, and the immunogenicity and possibility of using these cell lysates as a vaccine were evaluated. RESULTS: STAT3-blocked whole HCC cell lysates inhibited tumor growth and tumorigenesis, and prolonged the survival of tumor-bearing mice...
November 7, 2017: Journal of Experimental & Clinical Cancer Research: CR
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