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T cell exhaustion

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https://www.readbyqxmd.com/read/28939757/pd-1-blockade-promotes-epitope-spreading-in-anticancer-cd8-t-cell-responses-by-preventing-fratricidal-death-of-subdominant-clones-to-relieve-immunodomination
#1
Arash Memarnejadian, Courtney E Meilleur, Christopher R Shaler, Khashayarsha Khazaie, Jack R Bennink, Todd D Schell, S M Mansour Haeryfar
The interactions between programmed death-1 (PD-1) and its ligands hamper tumor-specific CD8(+) T cell (TCD8) responses, and PD-1-based "checkpoint inhibitors" have shown promise in certain cancers, thus revitalizing interest in immunotherapy. PD-1-targeted therapies reverse TCD8 exhaustion/anergy. However, whether they alter the epitope breadth of TCD8 responses remains unclear. This is an important question because subdominant TCD8 are more likely than immunodominant clones to escape tolerance mechanisms and may contribute to protective anticancer immunity...
September 22, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28935468/function-and-regulation-of-lag3-on-cd4-cd25-t-cells-in-non-small-cell-lung-cancer
#2
Qin-Yun Ma, Da-Yu Huang, Hui-Jun Zhang, Shaohua Wang, Xiao-Feng Chen
LAG3 is a surface molecule found on a subset of immune cells. The precise function of LAG3 appears to be context-dependent. In this study, we investigated the effect of LAG3 on CD4(+)CD25(-) T cells from non-small cell lung cancer (NSCLC) patients. We found that in the peripheral blood mononuclear cells of NSCLC patients, LAG3 was significantly increased in CD4(+) T cells directly ex vivo and primarily in the CD4(+)CD25(-) fraction, which was regulated by prolonged TCR stimulation and the presence of IL-27...
September 19, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28934428/hiv-infected-children-have-elevated-levels-of-pd-1-memory-cd4-t-cells-with-low-proliferative-capacity-and-high-inflammatory-cytokine-effector-functions
#3
Julia Foldi, Lina Kozhaya, Bret McCarty, Mussa Mwamzuka, Fatma Marshed, Tiina Ilmet, Max Kilberg, Adam Kravietz, Aabid Ahmed, William Borkowsky, Derya Unutmaz, Alka Khaitan
Background: During human immunodeficiency virus (HIV) disease, chronic immune activation leads to T-cell exhaustion. PD-1 identifies "exhausted" CD8 T cells with impaired HIV-specific effector functions, but its role on CD4 T cells and in HIV-infected children is poorly understood. Methods: In a Kenyan cohort of vertically HIV-infected children, we measured PD-1+ CD4 T-cell frequencies and phenotype by flow cytometry and their correlation with HIV disease progression and immune activation...
September 15, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28929191/overview-of-lag-3-expressing-il-10-producing-regulatory-t-cells
#4
Keishi Fujio, Kazuhiko Yamamoto, Tomohisa Okamura
Regulatory T cells (Treg cells) play crucial roles in the induction of peripheral tolerance to self- and foreign-antigens. IL-10-producing regulatory T cells (IL-10-producing Treg cells) constitute a Treg cell subset characterized by the production of high amounts of IL-10, cytokine-mediated immunosuppressive capabilities, and independence of Foxp3 expression for their suppressive activity. In the past decade, identifying naturally occurring IL-10-producing Treg cells was difficult due to the lack of suitable surface markers...
September 20, 2017: Current Topics in Microbiology and Immunology
https://www.readbyqxmd.com/read/28922790/the-balance-between-cytotoxic-t-cell-lymphocytes-and-immune-checkpoint-expression-in-the-prognosis-of-colon-tumors
#5
Laetitia Marisa, Magali Svrcek, Ada Collura, Etienne Becht, Pascale Cervera, Kristell Wanherdrick, Olivier Buhard, Anastasia Goloudina, Vincent Jonchère, Janick Selves, Gerard Milano, Dominique Guenot, Romain Cohen, Chrystelle Colas, Pierre Laurent-Puig, Sylviane Olschwang, Jérémie H Lefèvre, Yann Parc, Valérie Boige, Côme Lepage, Thierry André, Jean-François Fléjou, Valentin Dérangère, François Ghiringhelli, Aurélien de Reynies, Alex Duval
Background: Immune checkpoint (ICK) expression might represent a surrogate measure of tumor-infiltrating T cell (CTL) exhaustion and therefore be a more accurate prognostic biomarker for colorectal cancer (CRC) patients than CTL enumeration as measured by the Immunoscore. Methods: The expression of ICKs, Th1, CTLs, cytotoxicity-related genes, and metagenes, including Immunoscore-like metagenes, were evaluated in three independent cohorts of CRC samples (260 microsatellite instable [MSI], 971 non-MSI)...
January 1, 2018: Journal of the National Cancer Institute
https://www.readbyqxmd.com/read/28921638/graft-infiltrating-pd-l1-hi-cross-dressed-dendritic-cells-regulate-anti-donor-t-cell-responses-in-mouse-liver-transplant-tolerance
#6
Yoshihiro Ono, Angelica Perez-Gutierrez, Toshimasa Nakao, Helong Dai, Geoffrey Camirand, Osamu Yoshida, Shinichiro Yokota, Donna Beer Stolz, Mark A Ross, Adrian E Morelli, David A Geller, Angus W Thomson
While a key role of cross-dressing has been established in immunity to viral infection and more recently in the instigation of transplant rejection, its role in tolerance is unclear. Here, we investigated the role of intra-graft dendritic cells (DC) and cross-dressing in mouse major histocompatibility complex (MHC)-mismatched liver transplant tolerance that occurs without therapeutic immunosuppression. While donor interstitial DC diminished rapidly following transplantation, they were replaced in the liver by host DC that peaked on postoperative day (POD) 7 and persisted indefinitely...
September 16, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28919989/cyclophosphamide-treatment-regulates-the-balance-of-functional-exhausted-tumor-specific-cd8-t-cells
#7
Aurélie Hanoteau, Coralie Henin, David Svec, Charlotte Bisilliat Donnet, Sébastien Denanglaire, Didier Colau, Pedro Romero, Oberdan Leo, Benoit Van den Eynde, Muriel Moser
An important question is how chemotherapy may (re-)activate tumor-specific immunity. In this study, we provide a phenotypic, functional and genomic analysis of tumor-specific CD8(+) T cells in tumor (P815)-bearing mice, treated or not with cyclophosphamide. Our data show that chemotherapy favors the development of effector-type lymphocytes in tumor bed, characterized by higher KLRG-1 expression, lower PD-1 expression and increased cytotoxicity. This suggests re-engagement of T lymphocytes into the effector program...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28917721/low-levels-of-the-immunoregulator-semaphorin-4d-cd100-in-sera-of-hiv-patients
#8
Z Vadas, D Elbirt, S Radian, S Bezalel-Rosenberg, K Mahlab-Guri, E Toubi, I Asher, Z Sthoeger
INTRODUCTION: Semaphorin-4D (CD100), generated by CD4/CD8 cells, plays an important role in T cells activation. It also regulates B cell differentiation via its receptor the CD72. Both have soluble forms - sCD100/sCD72. METHODS: sCD100 and sCD72 levels were determined by ELISA (MyBioSource, USA). RESULTS: 28 chronic HIV patients and 50 matched healthy volunteers participated in our study. Before treatment, CD4 cell counts were 267±216cells/mcl and viral load (VL) was 586,675±1,897,431copies/ml...
September 13, 2017: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/28904066/pd-1-status-in-cd8-t-cells-associates-with-survival-and-anti-pd-1-therapeutic-outcomes-in-head-and-neck-cancer
#9
Benjamin A Kansy, Fernando Concha-Benavente, Raghvendra M Srivastava, Hyun-Bae Jie, Gulidanna Shayan, Yu Lei, Jessica Moskovitz, Jennifer Moy, Jing Li, Sven Brandau, Stephan Lang, Nicole C Schmitt, Gordon J Freeman, William E Gooding, David A Clump, Robert L Ferris
Improved understanding of expression of immune checkpoint receptors (ICR) on tumor-infiltrating lymphocytes (TIL) may facilitate more effective immunotherapy in head and neck cancer (HNC) patients. A higher frequency of PD-1(+) TIL has been reported in human papillomavirus (HPV)(+) HNC patients, despite the role of PD-1 in T cell exhaustion. This discordance led us to hypothesize that the extent of PD-1 expression more accurately defines T cell function and prognostic impact, since PD-1(high) T cells may be more exhausted than PD-1(low) T cells and may influence clinical outcome and response to anti-PD-1 immunotherapy...
September 13, 2017: Cancer Research
https://www.readbyqxmd.com/read/28903034/piwi-is-required-to-limit-exhaustion-of-aging-somatic-stem-cells
#10
Pedro Sousa-Victor, Arshad Ayyaz, Rippei Hayashi, Yanyan Qi, David T Madden, Victoria V Lunyak, Heinrich Jasper
Sophisticated mechanisms that preserve genome integrity are critical to ensure the maintenance of regenerative capacity while preventing transformation of somatic stem cells (SCs), yet little is known about mechanisms regulating genome maintenance in these cells. Here, we show that intestinal stem cells (ISCs) induce the Argonaute family protein Piwi in response to JAK/STAT signaling during acute proliferative episodes. Piwi function is critical to ensure heterochromatin maintenance, suppress retrotransposon activation, and prevent DNA damage in homeostasis and under regenerative pressure...
September 12, 2017: Cell Reports
https://www.readbyqxmd.com/read/28900926/immunological-disorders-regulation-of-ca-2-signaling-in-t-lymphocytes
#11
Sonal Srikanth, Jin Seok Woo, Zuoming Sun, Yousang Gwack
Engagement of T cell receptors (TCRs) with cognate antigens triggers cascades of signaling pathways in helper T cells. TCR signaling is essential for the effector function of helper T cells including proliferation, differentiation, and cytokine production. It also modulates effector T cell fate by inducing cell death, anergy (nonresponsiveness), exhaustion, and generation of regulatory T cells. One of the main axes of TCR signaling is the Ca(2+)-calcineurin-nuclear factor of activated T cells (NFAT) signaling pathway...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28899767/effects-of-hexavalent-chromium-on-mouse-splenic-t-lymphocytes
#12
Lu Dai, Wenhua Xu, Hui Li, Jacqueline A Frank, Caigu He, Zhuo Zhang, Gang Chen
Hexavalent chromium [Cr(VI)] is widely used in various industrial processes and has been recognized as a carcinogen. As the first line of host defense system, the immune system can be a primary target of Cr(VI). T cell population represents a major arm of the immune system that plays a critical role in host anti-tumor immunity. Dysfunction of T cells, such as exhaustion under the persistent presence of tumor antigen, compromise host anti-tumor immunity resulting in oncogenesis. Previous studies have shown Cr(VI) exposure alters the phenotype of human peripheral blood lymphocytes...
September 9, 2017: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/28894272/t-cell-tolerance-and-exhaustion-in-the-clearance-of-echinococcus-multilocularis-role-of-inoculum-size-in-a-quantitative-hepatic-experimental-model
#13
Chuanshan Zhang, Yingmei Shao, Shuting Yang, Xiaojuan Bi, Liang Li, Hui Wang, Ning Yang, Zhide Li, Cheng Sun, Liang Li, Guodong Lü, Tuerganaili Aji, Dominique A Vuitton, Renyong Lin, Hao Wen
The local immune mechanisms responsible for either self-healing or sustained chronic infection are not clear, in the development of E. multilocularis larvae. Here, we developed a suitable experimental model that mimics naturally infected livers, according to the parasite load. We demonstrated that local cellular immunity and fibrogenesis are actually protective and fully able to limit metacestode growth in the liver of low or medium dose-infected mice (LDG or MDG), or even to clear it, while impairment of cellular immunity is followed by a more rapid and severe course of the disease in high dose-infected mice (HDG)...
September 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28893274/modulation-of-the-strength-and-character-of-hiv-specific-cd8-t-cell-responses-with-heteroclitic-peptides
#14
REVIEW
Kayla A Holder, Michael D Grant
Chronic infection with human immunodeficiency virus (HIV) causes HIV-specific CD8(+) T cell dysfunction and exhaustion. The strong association between non-progression and maintenance of HIV-specific CD8(+) T cell cytokine production and proliferative capacities suggests that invigorating CD8(+) T cell immune responses would reduce viremia and slow disease progression. A series of studies have demonstrated that sequence variants of native immunogenic peptides can generate more robust CD8(+) T cell responses and that stimulation with these 'heteroclitic' peptides can steer responses away from the phenotypic and functional attributes of exhaustion acquired during chronic HIV infection...
September 12, 2017: AIDS Research and Therapy
https://www.readbyqxmd.com/read/28890544/mir-31-a-key-player-in-cd8-t-cell-exhaustion
#15
Siddheshvar Bhela, Barry T Rouse
No abstract text is available yet for this article.
September 11, 2017: Cellular & Molecular Immunology
https://www.readbyqxmd.com/read/28890294/analysis-of-non-small-cell-lung-cancer-microenvironment-indicates-preponderance-of-t-cell-exhaustion-marker-expression
#16
Hui Zhou, Tingwei Liu, Zanfeng Wang
Lung cancer metastasis causes 70% of an estimated 1.4 million deaths per annum. The major shortcoming in lung cancer is the tendency to have inherent or develop acquired resistance to chemotherapy. It is now evolving that such resistance might develop due to differential contribution and interaction with tumor microenvironment, stromal cells, and the extracellular matrix. The objective of the current study was to define the lung cancer tumor microenvironment. We have identified multiple tumor-infiltrating T lymphocyte subsets in patients with lung cancer, which were independent of disease stage...
September 8, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28886065/hepatitis-c-virus-mediated-chronic-inflammation-and-tumorigenesis-in-the-humanised-immune-system-and-liver-mouse-model
#17
Zhiqiang Zheng, Ching Wooen Sze, Choong Tat Keng, Muthafar Al-Haddawi, Min Liu, Sue Yee Tan, Hwee Ling Kwek, Zhisheng Her, Xue Ying Chan, Bhaskar Barnwal, Eva Loh, Kenneth Tou En Chang, Thiam Chye Tan, Yee-Joo Tan, Qingfeng Chen
Hepatitis C is a liver disease caused by infection of the Hepatitis C virus (HCV). Many individuals infected by the virus are unable to resolve the viral infection and develop chronic hepatitis, which can lead to formation of liver cirrhosis and cancer. To understand better how initial HCV infections progress to chronic liver diseases, we characterised the long term pathogenic effects of HCV infections with the use of a humanised mouse model (HIL mice) we have previously established. Although HCV RNA could be detected in infected mice up to 9 weeks post infection, HCV infected mice developed increased incidences of liver fibrosis, granulomatous inflammation and tumour formation in the form of hepatocellular adenomas or hepatocellular carcinomas by 28 weeks post infection compared to uninfected mice...
2017: PloS One
https://www.readbyqxmd.com/read/28883511/cytotoxic-response-against-epstein-barr-virus-coexists-with-diffuse-large-b-cell-lymphoma-tolerogenic-microenvironment-clinical-features-and-survival-impact
#18
Melina Cohen, Aldana G Vistarop, Fuad Huaman, Marina Narbaitz, Fernanda Metrebian, Elena De Matteo, María V Preciado, Paola A Chabay
Epstein-Barr Virus (EBV) is present in neoplastic cells of 15% of Asian and Latin-American diffuse large B-cell lymphoma (DLBCL) patients. Even though a tolerogenic microenvironment was recently described in DLBCL, little is known concerning immunomodulatory features induced by EBV. As suggested in Hodgkin lymphoma, EBV-specific cytotoxic T-cells are increased but showing immune exhaustion features. Hence, host immunity suppression may play a critical role in tumor progression. This study aimed to investigate, whether an association between tumor microenvironment features and EBV presence is taking place, and its clinical correlate...
September 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28883004/cd155t-tigit-signaling-regulates-cd8-t-cell-metabolism-and-promotes-tumor-progression-in-human-gastric-cancer
#19
Wei-Ling He, Hui Zhang, Fei Han, Xin-Lin Chen, Run Lin, Wei Wang, Hai-Bo Qiu, Zhenhong Zhuang, Qi Liao, Weijing Zhang, Qinbo Cai, Yongmei Cui, Wenting Jiang, Han Wang, Zunfu Ke
The T cell surface molecule TIGIT is an immune checkpoint molecule that inhibits T cell responses, but its roles in cancer are little understood. In this study, we evaluated the role TIGIT checkpoint plays in the development and progression of gastric cancer (GC). We show that the percentage of CD8 T cells that are TIGIT+ was increased in GC patients compared to healthy individuals. These cells showed functional exhaustion with impaired activation, proliferation, cytokine production and metabolism, all of which were rescued by glucose...
September 7, 2017: Cancer Research
https://www.readbyqxmd.com/read/28882621/antibodies-targeting-btla-or-tim-3-enhance-hiv-1-specific-t-cell-responses-in-combination-with-pd-1-blockade
#20
Katharina Grabmeier-Pfistershammer, Carmen Stecher, Markus Zettl, Sandra Rosskopf, Armin Rieger, Gerhard J Zlabinger, Peter Steinberger
Persistent stimulation with antigens derived from viruses that establish chronic infections or tumour antigens results in the exhaustion of T cells. Coinhibitory receptors like PD-1 and CTLA-4 function as immune checkpoints on exhausted T cells. Blocking these molecules with antibodies improve immunity to cancer cells. Immune checkpoint inhibitors targeting other coinhibitory receptors might have a similar role in improving T cell function and thus also utility in cancer therapy. Using HIV-specific T cells as a model for exhaustion we have evaluated the capacity of antibodies targeting TIM-3, BTLA, CD160, LAG-3 and CTLA-4 alone or in combination with a PD-1 antibody to enhance proliferation and cytokine production in response to Gag and Nef peptides...
September 4, 2017: Clinical Immunology: the Official Journal of the Clinical Immunology Society
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