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https://www.readbyqxmd.com/read/29786112/ctla%C3%A2-4-interferes-with-the-hbv%C3%A2-specific-t-cell-immune-response-review
#1
Hui Cao, Ruiwen Zhang, Wei Zhang
Hepatitis B virus (HBV) infection is a major cause of hepatic inflammation. Successful HBV clearance in patients is associated with sustained viral control by effector T cells. Compared with acute hepatitis B, chronic HBV infection is associated with the depletion of T cells, resulting in weak or absent virus‑specific T cells reactivity, which is described as 'exhaustion'. This exhaustion is characterized by impaired cytokine production and sustained expression of multiple coinhibitory molecules. Cytotoxic T lymphocyte‑associated antigen‑4 (CTLA‑4) is one of many coinhibitory molecules that can attenuate T cell activation by inhibiting costimulation and transmitting inhibitory signals to T cells...
May 17, 2018: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29703758/immune-checkpoint-inhibitor-induced-gastrointestinal-and-hepatic-injury-pathologists-perspective
#2
REVIEW
Dipti M Karamchandani, Runjan Chetty
Immune checkpoint inhibitors (CPIs) are a relatively new class of 'miracle' dugs that have revolutionised the treatment and prognosis of some advanced-stage malignancies, and have increased the survival rates significantly. This class of drugs includes cytotoxic T lymphocyte antigen-4 inhibitors such as ipilimumab; programmed cell death protein-1 inhibitors such as nivolumab, pembrolizumab and avelumab; and programmed cell death protein ligand-1 inhibitors such as atezolizumab. These drugs stimulate the immune system by blocking the coinhibitory receptors on the T cells and lead to antitumoural response...
April 27, 2018: Journal of Clinical Pathology
https://www.readbyqxmd.com/read/29669930/tsc2-deficient-tumors-have-evidence-of-t-cell-exhaustion-and-respond-to-anti-pd-1-anti-ctla-4-immunotherapy
#3
Heng-Jia Liu, Patrick H Lizotte, Heng Du, Maria C Speranza, Hilaire C Lam, Spencer Vaughan, Nicola Alesi, Kwok-Kin Wong, Gordon J Freeman, Arlene H Sharpe, Elizabeth P Henske
Tuberous sclerosis complex (TSC) is an incurable multisystem disease characterized by mTORC1-hyperactive tumors. TSC1/2 mutations also occur in other neoplastic disorders, including lymphangioleiomyomatosis (LAM) and bladder cancer. Whether TSC-associated tumors will respond to immunotherapy is unknown. We report here that the programmed death 1 coinhibitory receptor (PD-1) is upregulated on T cells in renal angiomyolipomas (AML) and pulmonary lymphangioleiomyomatosis (LAM). In C57BL/6J mice injected with syngeneic TSC2-deficient cells, anti-PD-1 alone decreased 105K tumor growth by 67% (P < 0...
April 19, 2018: JCI Insight
https://www.readbyqxmd.com/read/29593314/oncofetal-gene-sall4-reactivation-by-hepatitis-b-virus-counteracts-mir-200c-in-pd-l1-induced-t-cell-exhaustion
#4
Cheng Sun, Peixiang Lan, Qiuju Han, Mei Huang, Zhihong Zhang, Geliang Xu, Jiaxi Song, Jinyu Wang, Haiming Wei, Jian Zhang, Rui Sun, Cai Zhang, Zhigang Tian
A chronic viral or tumor microenvironment can push T cells to exhaustion by promoting coinhibitory ligand expression. However, how host factors control coinhibitory ligand expression and whether viral infection breaks this control during tumor progress is unknown. Here we show a close negative correlation between SALL4 or PD-L1 and miR-200c in tumors from 98 patients with HBV-related hepatocellular carcinoma. SALL4 or PD-L1 expression correlates negatively with miR-200c expression, and patients with lower levels of SALL4 or PD-L1 and higher miR-200c survive longer...
March 28, 2018: Nature Communications
https://www.readbyqxmd.com/read/29577049/the-influence-of-genetic-variations-in-the-cd86-gene-on-the-outcome-after-allogeneic-hematopoietic-stem-cell-transplantation
#5
Lidia Karabon, Miroslaw Markiewicz, Karolina Chrobot, Monika Dzierzak-Mietla, Edyta Pawlak-Adamska, Anna Partyka, Anna Koclega, Slawomira Kyrcz-Krzemien, Irena Frydecka
CD86 molecule is the ligand for both costimulatory (CD28) and coinhibitory (CTLA-4) molecules, and it regulates immune response after allogeneic hematopoietic stem cell transplantation (alloHSCT). Therefore, we postulate that CD86 gene variations might influence the outcome after alloHSCT. Altogether, 295 adult patients (pts) undergoing related (105 pts) and unrelated (190 pts) donor-matched HSCT were genotyped for the following CD86 gene polymorphisms: rs1129055, rs9831894, and rs2715267. Moreover, the donors' rs1129055 polymorphism was determined...
2018: Journal of Immunology Research
https://www.readbyqxmd.com/read/29531164/dendritic-cell-pd-l1-limits-autoimmunity-and-follicular-t-cell-differentiation-and-function
#6
Peter T Sage, Frank A Schildberg, Raymond A Sobel, Vijay K Kuchroo, Gordon J Freeman, Arlene H Sharpe
The programmed death (PD)-1 coinhibitory receptor regulates the balance between T cell activation and tolerance. Although the PD-1 ligands, PD-L1 and PD-L2, are expressed on a variety of cell types, the cell type-specific functions of PD-1 ligands in inducing signals through PD-1 are unknown. In this study, we use PD-L1 conditional knockout mice to investigate the cell type-specific functions of PD-L1. We demonstrate that PD-L1 expressed on dendritic cells (DCs), and to a lesser extent on B cells, attenuates the progression of experimental autoimmune encephalomyelitis and inhibits naive and effector T cells...
April 15, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29520282/checks-and-balances-in-autoimmune-vasculitis
#7
Rebeca Hid Cadena, Wayel H Abdulahad, G A P Hospers, T T Wind, Annemieke M H Boots, Peter Heeringa, Elisabeth Brouwer
Age-associated changes in the immune system including alterations in surface protein expression are thought to contribute to an increased susceptibility for autoimmune diseases. The balance between the expression of coinhibitory and costimulatory surface protein molecules, also known as immune checkpoint molecules, is crucial in fine-tuning the immune response and preventing autoimmunity. The activation of specific inhibitory signaling pathways allows cancer cells to evade recognition and destruction by the host immune system...
2018: Frontiers in Immunology
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...
April 15, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29473504/immunotherapy-in-non-small-cell-lung-cancer-biological-principles-and-future-opportunities
#9
M Ilie, J Benzaquen, V Hofman, S Lassalle, N Yazbeck, S Leroy, S Heeke, C Bence, B Mograbi, N Glaichenhaus, C-H Marquette, P Hofman
Immunotherapy aims to amplify the anticancer immune response through reactivation of the lymphocytic response raised against several tumor neo-antigens. To obtain an effective immune response, this therapeutic approach requires that a number of immunological checkpoints be passed, such as the activation of excitatory costimulatory signals or the avoidance of coinhibitory molecules. Among the immune checkpoints, the interaction of the membrane-bound ligand PD-1 and its receptor PD-L1 has received much attention because of remarkable efficacy in numerous clinical trials for various cancer types, including non-small cell lung cancer (NSCLC)...
2017: Current Molecular Medicine
https://www.readbyqxmd.com/read/29393983/a-novel-role-for-coinhibitory-receptors-checkpoint-proteins-in-the-immunopathology-of-sepsis
#10
REVIEW
Eleanor A Fallon, Bethany M Biron-Girard, Chun-Shiang Chung, Joanne Lomas-Neira, Daithi S Heffernan, Sean F Monaghan, Alfred Ayala
Coinhibitory molecules, such as PD-1, CTLA-4, 2B4, and BTLA, are an important new family of mediators in the pathophysiology of severe bacterial and/or fungal infection, as well as the combined insults of shock and sepsis. Further, the expression of these molecules may serve as indicators of the immune status of the septic individual. Using PD-1:PD-L as an example, we discuss in this review how such checkpoint molecules may affect the host response to infection by mediating the balance between effective immune defense and immune-mediated tissue injury...
February 2, 2018: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/29360721/preclinical-data-supporting-antitumor-activity-of-pd-1-blockade
#11
Michael A Curran
Antibodies that block the PD-1 coinhibitory receptor on T cells or its primary ligand, PD-L1, have demonstrated unprecedented efficacy across a diverse array of both solid and hematologic malignancies in the clinic. These advances were built on a foundation of murine preclinical tumor model studies, which both demonstrated the therapeutic potential of PD-1/PD-L1 antibody blockade and also provided critical insights into the cellular and molecular processes underlying their capacity to elicit immune-mediated tumor regressions...
January 2018: Cancer Journal
https://www.readbyqxmd.com/read/29313945/endocrine-dysfunction-induced-by-immune-checkpoint-inhibitors-practical-recommendations-for-diagnosis-and-clinical-management
#12
REVIEW
Romualdo Barroso-Sousa, Patrick A Ott, F Stephen Hodi, Ursula B Kaiser, Sara M Tolaney, Le Min
Immune checkpoint inhibitors (ICIs) have revolutionized cancer therapy. However, because ICIs block coinhibitory molecules on T cells and other immune cells, unleashing them to mediate tumor cell killing, they also can disrupt the maintenance of immunological tolerance to self-antigens. Compared with chemotherapy, ICIs have a different toxicity profile, especially the occurrence of autoimmune-like manifestations against multiple organ systems, including endocrine glands, commonly referred to as immune-related adverse events...
March 15, 2018: Cancer
https://www.readbyqxmd.com/read/29259116/mixed-signature-of-activation-and-dysfunction-allows-human-decidual-cd8-t-cells-to-provide-both-tolerance-and-immunity
#13
Anita van der Zwan, Kevin Bi, Errol R Norwitz, Ângela C Crespo, Frans H J Claas, Jack L Strominger, Tamara Tilburgs
Understanding how decidual CD8+ T cell (CD8+ dT) cytotoxicity is regulated and how these cells integrate the competing needs for maternal-fetal tolerance and immunity to infection is an important research and clinical goal. Gene-expression analysis of effector-memory CD8+ dT demonstrated a mixed transcriptional signature of T cell dysfunction, activation, and effector function. High protein expression of coinhibitory molecules PD1, CTLA4, and LAG3, accompanied by low expression of cytolytic molecules suggests that the decidual microenvironment reduces CD8+ dT effector responses to maintain tolerance to fetal antigens...
January 9, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29212910/foxp1-negatively-regulates-t-follicular-helper-cell-differentiation-and-germinal-center-responses-by-controlling-cell-migration-and-ctla-4
#14
Bi Shi, Jianlin Geng, Yin-Hu Wang, Hairong Wei, Beth Walters, Wei Li, Xuerui Luo, Anna Stevens, Melanie Pittman, Bin Li, Sunnie R Thompson, Hui Hu
T follicular helper (Tfh) cells play an essential role in the formation of germinal centers (GC) and generation of high-affinity Abs. The homing of activated CD4+ T cells into B cell follicles and the involvement of key costimulatory and coinhibitory molecules are critical in controlling both the initiation and the magnitude of GC responses. Meanwhile, studies have shown that a high number of single clone B cells leads to intraclonal competition, which inhibits the generation of high-affinity Abs. Our previous work has shown that transcription factor Foxp1 is a critical negative regulator of Tfh cell differentiation...
January 15, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29180838/suppressed-programmed-death-1-expression-on-cd4-and-cd8-t-cells-in-psoriatic-patients
#15
Joanna Bartosińska, Ewelina Zakrzewska, Dorota Raczkiewicz, Joanna Purkot, Anna Michalak-Stoma, Małgorzata Kowal, Dorota Krasowska, Grażyna Chodorowska, Krzysztof Giannopoulos
Psoriasis is a chronic inflammatory disease mediated by T cell immunity. Programmed death 1 (PD-1), a coinhibitory receptor, plays an important role in immune regulation and maintaining peripheral tolerance. The aim of the study was to compare the expression of PD-1 on the peripheral T cells between psoriatic patients and healthy controls. The study included 75 psoriatic patients and 52 healthy volunteers. The percentages and absolute numbers of CD3+ , CD4+ , CD8+ , CD4+ PD-1+ , and CD8+ PD-1+ T cells were analyzed using flow cytometry...
2017: Mediators of Inflammation
https://www.readbyqxmd.com/read/29137299/tumor-expressed-immune-checkpoint-b7x-promotes-cancer-progression-and-antigen-specific-cd8-t-cell-exhaustion-and-suppressive-innate-immune-cells
#16
Kim C Ohaegbulam, Weifeng Liu, Hyungjun Jeon, Steven C Almo, Xingxing Zang
B7x (B7-H4 or B7S1) is a coinhibitory member of the B7 immune checkpoint ligand family that regulates immune function following ligation with its unknown cognate receptors. B7x has limited expression on normal tissues, but is up-regulated on solid human tumors to inhibit anti-tumor immunity and associates with poor clinical prognosis. We assessed the contribution of cytokine stimuli to induce surface B7x expression on cancer cells and the role of tumor-expressed B7x in a murine pulmonary metastasis model, and finally evaluated the potential interaction between B7x and Neuropilin-1, a suggested potential cognate receptor...
October 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29126798/cd4-t-cell-help-confers-a-cytotoxic-t-cell-effector-program-including-coinhibitory-receptor-downregulation-and-increased-tissue-invasiveness
#17
Tomasz Ahrends, Aldo Spanjaard, Bas Pilzecker, Nikolina Bąbała, Astrid Bovens, Yanling Xiao, Heinz Jacobs, Jannie Borst
CD4+ T cells optimize the cytotoxic T cell (CTL) response in magnitude and quality, by unknown molecular mechanisms. We here present the transcriptomic changes in CTLs resulting from CD4+ T cell help after anti-cancer vaccination or virus infection. The gene expression signatures revealed that CD4+ T cell help during priming optimized CTLs in expression of cytotoxic effector molecules and many other functions that ensured efficacy of CTLs throughout their life cycle. Key features included downregulation of PD-1 and other coinhibitory receptors that impede CTL activity, and increased motility and migration capacities...
November 21, 2017: Immunity
https://www.readbyqxmd.com/read/29109121/glycogen-synthase-kinase-3-modulates-cbl-b-and-constrains-t-cell-activation
#18
Charles W Tran, Samuel D Saibil, Thierry Le Bihan, Sara R Hamilton, Karl S Lang, Han You, Amy E Lin, Kristine M Garza, Alisha R Elford, Kelly Tai, Michael E Parsons, Kip Wigmore, Mitchell G Vainberg, Josef M Penninger, James R Woodgett, Tak W Mak, Pamela S Ohashi
The decision between T cell activation and tolerance is governed by the spatial and temporal integration of diverse molecular signals and events occurring downstream of TCR and costimulatory or coinhibitory receptor engagement. The PI3K-protein kinase B (PKB; also known as Akt) signaling pathway is a central axis in mediating proximal signaling events of TCR and CD28 engagement in T cells. Perturbation of the PI3K-PKB pathway, or the loss of negative regulators of T cell activation, such as the E3 ubiquitin ligase Cbl-b, have been reported to lead to increased susceptibility to autoimmunity...
December 15, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29101312/gingival-tissue-inflammation-promotes-increased-matrix-metalloproteinase-12-production-by-cd200r-low-monocyte-derived-cells-in-periodontitis
#19
Sofia Björnfot Holmström, Reuben Clark, Stephanie Zwicker, Daniela Bureik, Egle Kvedaraite, Eric Bernasconi, Anh Thu Nguyen Hoang, Gunnar Johannsen, Benjamin J Marsland, Elisabeth A Boström, Mattias Svensson
Irreversible tissue recession in chronic inflammatory diseases is associated with dysregulated immune activation and production of tissue degradative enzymes. In this study, we identified elevated levels of matrix metalloproteinase (MMP)-12 in gingival tissue of patients with the chronic inflammatory disease periodontitis (PD). The source of MMP12 was cells of monocyte origin as determined by the expression of CD14, CD68, and CD64. These MMP12-producing cells showed reduced surface levels of the coinhibitory molecule CD200R...
December 15, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29099676/molecular-and-genomic-determinants-of-response-to-immune-checkpoint-inhibition-in-cancer
#20
Russell W Jenkins, Rohit Thummalapalli, Jacob Carter, Israel Cañadas, David A Barbie
Molecularly targeted therapy and immunotherapy have dramatically changed the landscape of available treatment options for patients with advanced cancer. Improved understanding of the molecular and genomic features of cancers over the last decade has led to the development of successful targeted therapies and the field of precision cancer medicine. As a result of these advances, patients whose tumors harbor select molecular alterations are eligible for treatment with targeted therapies active against the unique molecular aberration...
January 29, 2018: Annual Review of Medicine
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