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Exhausted T cell

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https://www.readbyqxmd.com/read/29679299/impact-of-computer-aided-ct-and-pet-analysis-on-non-invasive-t-staging-in-patients-with-lung-cancer-and-atelectasis
#1
Paul Flechsig, Ramin Rastgoo, Clemens Kratochwil, Ole Martin, Tim Holland-Letz, Alexander Harms, Hans-Ulrich Kauczor, Uwe Haberkorn, Frederik L Giesel
PURPOSE: Tumor delineation within an atelectasis in lung cancer patients is not always accurate. When T staging is done by integrated 2-deoxy-2-[18 F]fluoro-D-glucose ([18 F]FDG)-positron emission tomography (PET)/X-ray computer tomography (CT), tumors of neuroendocrine differentiation and slowly growing tumors can present with reduced FDG uptake, thus aggravating an exact T staging. In order to further exhaust information derived from [18 F]FDG-PET/CT, we evaluated the impact of CT density and maximum standardized uptake value (SUVmax) for the classification of different tumor subtypes within a surrounding atelectasis, as well as possible cutoff values for the differentiation between the primary tumor and atelectatic lung tissue...
April 20, 2018: Molecular Imaging and Biology: MIB: the Official Publication of the Academy of Molecular Imaging
https://www.readbyqxmd.com/read/29675979/senescent-cells-re-engineered-to-express-spd-1-for-inhibiting-pd-1-pd-l1-as-a-vaccination-approach-against-breast-cancer
#2
Zehong Chen, Kang Hu, Lieting Feng, Ruxiong Su, Nan Lai, Zike Yang, Shijun Kang
Various types of vaccines have been proposed as approaches for prevention or delay of the onset of cancer by boosting the endogenous immune system. We previously developed a senescent-cell-based vaccine, induced by radiation and veliparib, as a preventive and therapeutic tool against triple-negative breast cancer. However, the PD-1/PD-L1 pathway was found to play an important role in vaccine failure. Hence, we further developed sPD1-expressing senescent cells to overcome PD-L1/PD1-mediated immune suppression while vaccinating to promote dendritic cells (DCs) maturity, thereby amplifying T cell activation...
April 20, 2018: Cancer Science
https://www.readbyqxmd.com/read/29672594/type-i-interferon-signaling-attenuates-regulatory-t-cell-function-in-viral-infection-and-in-the-tumor-microenvironment
#3
Arunakumar Gangaplara, Craig Martens, Eric Dahlstrom, Amina Metidji, Ameya S Gokhale, Deborah D Glass, Maria Lopez-Ocasio, Rachel Baur, Kishore Kanakabandi, Stephen F Porcella, Ethan M Shevach
Regulatory T cells (Tregs) play a cardinal role in the immune system by suppressing detrimental autoimmune responses, but their role in acute, chronic infectious diseases and tumor microenvironment remains unclear. We recently demonstrated that IFN-α/β receptor (IFNAR) signaling promotes Treg function in autoimmunity. Here we dissected the functional role of IFNAR-signaling in Tregs using Treg-specific IFNAR deficient (IFNARfl/flxFoxp3YFP-Cre) mice in acute LCMV Armstrong, chronic Clone-13 viral infection, and in tumor models...
April 19, 2018: PLoS Pathogens
https://www.readbyqxmd.com/read/29671161/under-evaluated-or-unassessed-pathogenic-pathways-in-autoimmune-hepatitis-and-implications-for-future-management
#4
REVIEW
Albert J Czaja
Autoimmune hepatitis is a consequence of perturbations in homeostatic mechanisms that maintain self-tolerance but are incompletely understood. The goals of this review are to describe key pathogenic pathways that have been under-evaluated or unassessed in autoimmune hepatitis, describe insights that may shape future therapies, and encourage investigational efforts. The T cell immunoglobulin mucin proteins constitute a family that modulates immune tolerance by limiting the survival of immune effector cells, clearing apoptotic bodies, and expanding the population of granulocytic myeloid-derived suppressor cells...
April 18, 2018: Digestive Diseases and Sciences
https://www.readbyqxmd.com/read/29670207/homeostatic-proliferation-leads-to-telomere-attrition-and-increased-pd-1-expression-after-autologous-hematopoietic-sct-for-systemic-sclerosis
#5
Lucas C M Arruda, João R Lima-Júnior, Emmanuel Clave, Daniela A Moraes, Corinne Douay, Isabelle Fournier, Hélène Moins-Teisserenc, Dimas T Covas, Belinda P Simões, Dominique Farge, Antoine Toubert, Kelen C R Malmegrim, Maria Carolina Oliveira
In the months that follow autologous hematopoietic stem cell transplantation (AHSCT), lymphopenia drives homeostatic proliferation, leading to oligoclonal expansion of residual cells. Here we evaluated how replicative senescent and exhausted cells associated with clinical outcomes of 25 systemic sclerosis (SSc) patients who underwent AHSCT. Patients were clinically monitored for skin (modified Rodnan's skin score, mRSS) and internal organ involvement and had blood samples collected before and semiannually, until 3 years post-AHSCT, for quantification of telomere length, CD8+ CD28- and PD-1+ cells, and serum cytokines...
April 18, 2018: Bone Marrow Transplantation
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
#6
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/29669251/self-renewal-and-toll-like-receptor-signaling-sustain-exhausted-plasmacytoid-dendritic-cells-during-chronic-viral-infection
#7
Monica Macal, Yeara Jo, Simone Dallari, Aaron Y Chang, Jihong Dai, Shobha Swaminathan, Ellen J Wehrens, Patricia Fitzgerald-Bocarsly, Elina I Zúñiga
Although characterization of T cell exhaustion has unlocked powerful immunotherapies, the mechanisms sustaining adaptations of short-lived innate cells to chronic inflammatory settings remain unknown. During murine chronic viral infection, we found that concerted events in bone marrow and spleen mediated by type I interferon (IFN-I) and Toll-like receptor 7 (TLR7) maintained a pool of functionally exhausted plasmacytoid dendritic cells (pDCs). In the bone marrow, IFN-I compromised the number and the developmental capacity of pDC progenitors, which generated dysfunctional pDCs...
April 17, 2018: Immunity
https://www.readbyqxmd.com/read/29666149/genetic-and-phenotypic-difference-in-cd8-t-cell-exhaustion-between-chronic-hepatitis-b-infection-and-hepatocellular-carcinoma
#8
Xiaochen Wang, Qifeng He, Haiyuan Shen, Xiao-Jie Lu, Beicheng Sun
BACKGROUND: Several recent studies published have suggested that T cell exhaustion exists both in chronic infection and cancer. However, to date, few studies have investigated their differences. Here we designed this study to explore the genetic and phenotypic difference in CD8+ T cell exhaustion between chronic hepatitis B (CHB) and hepatocellular carcinoma (HCC). METHODS: In this study, we assayed the phenotypes and functional states of CD8+ T cells separating from human CHB tissues and HCC tissues, and re-analyse the single-cell sequencing data (GSE98638) published previously...
April 17, 2018: Journal of Medical Genetics
https://www.readbyqxmd.com/read/29664577/the-gradual-rise-of-memory-inflation
#9
REVIEW
Paul Klenerman
Memory inflation, as a term, has been used for 15 years now to describe the longitudinal development of stable, expanded CD8+ T memory pools with a distinct phenotype and functional profile which emerge in specific infection and vaccine settings. These settings have in common the persistence of antigen, especially cytomegalovirus infection but also more recently adenoviral vector vaccination. However, in contrast to chronic infections which lead to "exhaustion" the repeated antigen encounters experienced by CD8+ T cells lead to development of a robust T-cell population structure which maintains functionality and size...
May 2018: Immunological Reviews
https://www.readbyqxmd.com/read/29663369/specific-blockade-cd73-alters-the-exhausted-phenotype-of-t-cells-in-head-and-neck-squamous-cell-carcinoma
#10
Wei-Wei Deng, Yi-Cun Li, Si-Rui Ma, Liang Mao, Guang-Tao Yu, Lin-Lin Bu, Ashok B Kulkarni, Wen-Feng Zhang, Zhi-Jun Sun
The adenosine-induced immunosuppression hampers the immune response toward tumor cells and facilitates the tumor cells to evade immunosurveillance. CD73, an ecto-5-nucleotidase, is the ectoenzyme dephosphorylating extracellular AMP to adenosine. Here, using immunocompetent transgenic head and neck squamous cell carcinoma (HNSCC) mouse model, immune profiling showed high expression of CD73 on CD4+ and CD8+ T cells was associated with an 'exhausted' phenotype. Further, treatment with anti-CD73 monoclonal antibody (mAb) significantly blunted the tumor growth in the mouse model, and the blockade of CD73 reversed the 'exhausted' phenotype of CD4+ and CD8+ T cells through downregulation of total expression of PD-1 and CTLA-4 on T cells...
April 16, 2018: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/29661773/integrated-genomic-and-immunophenotypic-classification-of-pancreatic-cancer-reveals-three-distinct-subtypes-with-prognostic-predictive-significance
#11
Martin Wartenberg, Silvia Cibin, Inti Zlobec, Erik Vassella, Serenella M M Eppenberger-Castori, Luigi Terracciano, Micha Eichmann, Mathias Worni, Beat Gloor, Aurel Perren, Eva Karamitopoulou
PURPOSE: Current clinical classification of pancreatic ductal adenocarcinoma (PDAC) is unable to predict prognosis or response to chemo- or immunotherapy and does not take into account the host reaction to PDAC-cells. Our aim is to classify PDAC according to host- and tumor-related factors into clinically/biologically relevant subtypes by integrating molecular and microenvironmental findings. EXPERIMENTAL DESIGN: A well-characterized PDAC-cohort (n=110) underwent next-generation sequencing with a hotspot cancer panel, while Next-generation Tissue-Microarrays were immunostained for CD3, CD4, CD8, CD20, PD-L1, p63, hyaluronan-mediated motility receptor (RHAMM) and DNA mismatch-repair proteins...
April 16, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29661225/lymphocyte-subset-expression-and-serum-concentrations-of-pd-1-pd-l1-in-sepsis-pilot-study
#12
Julie K Wilson, Yuan Zhao, Mervyn Singer, Jo Spencer, Manu Shankar-Hari
BACKGROUND: Sepsis remains a major cause of mortality in critical care, for which specific treatments are lacking. The dysregulated response to infection seen in sepsis includes features of lymphocyte dysfunction and exhaustion, suggesting that immune-stimulatory therapy may improve outcomes in certain patient groups. Monoclonal antibodies targeting checkpoint molecules, such as programmed-death 1 protein (PD-1) and its ligand PD-L1, have shown success in stimulating the immune response in patients with cancer, and are being considered for future sepsis trials...
April 17, 2018: Critical Care: the Official Journal of the Critical Care Forum
https://www.readbyqxmd.com/read/29656492/pd-1-blockade-cellular-vesicles-for-cancer-immunotherapy
#13
Xudong Zhang, Chao Wang, Jinqiang Wang, Quanyin Hu, Benjamin Langworthy, Yanqi Ye, Wujin Sun, Jing Lin, Tianfu Wang, Jason Fine, Hao Cheng, Gianpietro Dotti, Peng Huang, Zhen Gu
Cancer cells resist to the host immune antitumor response via multiple suppressive mechanisms, including the overexpression of PD-L1 that exhausts antigen-specific CD8+ T cells through PD-1 receptors. Checkpoint blockade antibodies against PD-1 or PD-L1 have shown unprecedented clinical responses. However, limited host response rate underlines the need to develop alternative engineering approaches. Here, engineered cellular nanovesicles (NVs) presenting PD-1 receptors on their membranes, which enhance antitumor responses by disrupting the PD-1/PD-L1 immune inhibitory axis, are reported...
April 14, 2018: Advanced Materials
https://www.readbyqxmd.com/read/29649617/reversal-of-t-cell-exhaustion-by-the-first-donor-lymphocyte-infusion-is-associated-with-the-persistently-effective-anti-leukemic-responses-in-patients-with-relapsed-aml-after-allo-hsct
#14
Long Liu, Ying-Jun Chang, Lan-Ping Xu, Xiao-Hui Zhang, Yu Wang, Kai-Yan Liu, Xiao-Jun Huang
Donor lymphocyte infusion is an effective approach to treat acute myeloid leukemia (AML) relapse after allogeneic hematopoietic stem cell transplantation (allo-HSCT) that significantly improves the survival of relapsed patients. However, the mechanism of an effective anti-leukemic response following DLI in AML relapse remains elusive. Here, we investigated the role of T cell exhaustion in AML relapse after allo-HSCT in prospective cohorts of 41 patients with the first AML relapse and 41 non-relapsed AML controls after allo-HSCT and determined whether DLI exerts effective anti-leukemic effects by reversing T cell exhaustion in the relapsed cohorts by detecting the phenotypes and functions of T cells using flow cytometry...
April 9, 2018: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/29644653/specific-blockade-cd73-alters-the-exhausted-phenotype-of-t-cells-in-head-and-neck-squamous-cell-carcinoma
#15
Wei-Wei Deng, Yi-Cun Li, Si-Rui Ma, Liang Mao, Guang-Tao Yu, Lin-Lin Bu, Ashok B Kulkarni, Wen-Feng Zhang, Zhi-Jun Sun
The adenosine-induced immunosuppression hampers the immune response toward tumor cells and facilitates the tumor cells to evade immunosurveillance. CD73, an ecto-5-nucleotidase, is the ectoenzyme dephosphorylating extracellular AMP to adenosine. Here, using immunocompetent transgenic head and neck squamous cell carcinoma (HNSCC) mouse model, immune profiling showed high expression of CD73 on CD4+ and CD8+ T cells was associated with an 'exhausted' phenotype. Further, treatment with anti-CD73 monoclonal antibody (mAb) significantly blunted the tumor growth in the mouse model, and the blockade of CD73 reversed the 'exhausted' phenotype of CD4+ and CD8+ T cells through downregulation of total expression of PD-1 and CTLA-4 on T cells...
April 12, 2018: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/29643231/personalized-cancer-vaccine-effectively-mobilizes-antitumor-t-cell-immunity-in-ovarian-cancer
#16
Janos L Tanyi, Sara Bobisse, Eran Ophir, Sandra Tuyaerts, Annalisa Roberti, Raphael Genolet, Petra Baumgartner, Brian J Stevenson, Christian Iseli, Denarda Dangaj, Brian Czerniecki, Aikaterini Semilietof, Julien Racle, Alexandra Michel, Ioannis Xenarios, Cheryl Chiang, Dimitri S Monos, Drew A Torigian, Harvey L Nisenbaum, Olivier Michielin, Carl H June, Bruce L Levine, Daniel J Powel, David Gfeller, Rosemarie Mick, Urania Dafni, Vincent Zoete, Alexandre Harari, George Coukos, Lana E Kandalaft
We conducted a pilot clinical trial testing a personalized vaccine generated by autologous dendritic cells (DCs) pulsed with oxidized autologous whole-tumor cell lysate (OCDC), which was injected intranodally in platinum-treated, immunotherapy-naïve, recurrent ovarian cancer patients. OCDC was administered alone (cohort 1, n = 5), in combination with bevacizumab (cohort 2, n = 10), or bevacizumab plus low-dose intravenous cyclophosphamide (cohort 3, n = 10) until disease progression or vaccine exhaustion. A total of 392 vaccine doses were administered without serious adverse events...
April 11, 2018: Science Translational Medicine
https://www.readbyqxmd.com/read/29625896/co-inhibitory-molecule-b7-superfamily-member-1-expressed-by-tumor-infiltrating-myeloid-cells-induces-dysfunction-of-anti-tumor-cd8-t-cells
#17
Jing Li, Younghee Lee, Yanjian Li, Yu Jiang, Huiping Lu, Wenjuan Zang, Xiaohong Zhao, Liguo Liu, Yang Chen, Haidong Tan, Zhiying Yang, Michael Q Zhang, Tak W Mak, Ling Ni, Chen Dong
The molecular mechanisms whereby CD8+ T cells become "exhausted" in the tumor microenvironment remain unclear. Programmed death ligand-1 (PD-L1) is upregulated on tumor cells and PD-1-PD-L1 blockade has significant efficacy in human tumors; however, most patients do not respond, suggesting additional mechanisms underlying T cell exhaustion. B7 superfamily member 1 (B7S1), also called B7-H4, B7x, or VTCN1, negatively regulates T cell activation. Here we show increased B7S1 expression on myeloid cells from human hepatocellular carcinoma correlated with CD8+ T cell dysfunction...
March 29, 2018: Immunity
https://www.readbyqxmd.com/read/29623180/pembrolizumab-and-its-role-in-relapsed-refractory-classical-hodgkin-s-lymphoma-evidence-to-date-and-clinical-utility
#18
REVIEW
Polina Shindiapina, Lapo Alinari
Immune evasion is a critical mechanism of malignant cell survival, and relies in part on molecular signaling through the programmed cell death 1 (PD-1)/PD-1 ligand (PD-L1) axis that contributes to T cell exhaustion. Immune modulatory therapy with monoclonal antibodies against PD-1 designed to enhance antitumor immune response have shown promise in the treatment of advanced solid tumors and hematologic malignancies. Classical Hodgkin's lymphoma (cHL), a unique B cell malignancy characterized by an extensive but ineffective immune cell infiltrate surrounding a small number of tumor cells, has shown significant response to anti-PD-1 directed therapy...
April 2018: Therapeutic Advances in Hematology
https://www.readbyqxmd.com/read/29620933/dynamics-of-lymphocyte-reconstitution-following-hematopoietic-transplantation-during-chronic-lcmv-infection
#19
Mitra Bhattacharyya, Pablo Penaloza-MacMaster
Bone marrow transplantation is a treatment for various cancers and genetic diseases, and the only case of cured a HIV infection involved the use of this clinical procedure, highlighting the potential use of this therapy for curing many chronic diseases. However, little is known about how chronic viral infection influences lymphocyte reconstitution after bone marrow transplantation. To address this, we infected mice with chronic lymphocytic choriomeningitis virus (LCMV), and performed bone marrow transplantation to assess lymphocyte reconstitution...
March 18, 2018: AIDS Research and Human Retroviruses
https://www.readbyqxmd.com/read/29619420/changes-in-natural-killer-cells-and-exhausted-memory-regulatory-t-cells-with-corticosteroid-therapy-in-acute-autoimmune-hepatitis
#20
Hannah C Jeffery, Manjit K Braitch, Chris Bagnall, James Hodson, Louisa E Jeffery, Rebecca E Wawman, Lin Lee Wong, Jane Birtwistle, Helen Bartlett, Ansgar W Lohse, Gideon M Hirschfield, Jessica Dyson, David Jones, Stefan G Hubscher, Paul Klenerman, David H Adams, Ye H Oo
Autoimmune hepatitis (AIH) is an immune-mediated liver disease currently treated by immunosuppressive medications with significant side effects. Thus, novel mechanistic treatments are greatly needed. We performed prospective deep immunophenotyping of blood immune cells in patients with acute AIH before and after corticosteroid therapy. Blood samples from 26 patients with acute AIH (United Kingdom-AIH Consortium) were phenotyped by flow cytometry at baseline and 4 months after starting corticosteroids. Pretreatment liver tissues were stained for forkhead box P3-positive (FOXP3POS ) regulatory T cells (Tregs), clusters of differentiation (CD)56POS natural killer (NK) cells, and chemokine (C-X-C motif) ligand 10...
April 2018: Hepatology communications
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