keyword
MENU ▼
Read by QxMD icon Read
search

Exhausted T cell

keyword
https://www.readbyqxmd.com/read/29456538/an-uncoupling-of-canonical-phenotypic-markers-and-functional-potency-of-ex-vivo-expanded-natural-killer-cells
#1
Nicole A P Lieberman, Kole DeGolier, Kristen Haberthur, Harrison Chinn, Kara W Moyes, Myriam N Bouchlaka, Kirsti L Walker, Christian M Capitini, Courtney A Crane
Recent advances in cellular therapies for patients with cancer, including checkpoint blockade and ex vivo -expanded, tumor-specific T cells, have demonstrated that targeting the immune system is a powerful approach to the elimination of tumor cells. Clinical efforts have also demonstrated limitations, however, including the potential for tumor cell antigenic drift and neoantigen formation, which promote tumor escape and recurrence, as well as rapid onset of T cell exhaustion in vivo . These findings suggest that antigen unrestricted cells, such as natural killer (NK) cells, may be beneficial for use as an alternative to or in combination with T cell based approaches...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29449693/tumor-cell-intrinsic-tim-3-promotes-liver-cancer-via-nf-%C3%AE%C2%BAb-il-6-stat3-axis
#2
Hualin Zhang, Yang Song, Huimin Yang, Zhiyan Liu, Lifen Gao, Xiaohong Liang, Chunhong Ma
T-cell immunoglobulin and mucin-domain containing-3 (Tim-3), mediating immune exhaustion in tumor microenvironment, has become a promising target for tumor therapy. However, the exact mechanisms for tumor cell-intrinsic Tim-3 in tumor development and its potential contribution in Tim-3-targeted therapy strategy have not been elucidated yet. In this study, we showed that human liver cancer tissues contained high ratio of Tim-3-expressing hepatocytes, and cytokines rich in tumor microenvironment and HBV involved in Tim-3 upregulation in malignant hepatocytes...
February 16, 2018: Oncogene
https://www.readbyqxmd.com/read/29449276/immune-evasion-via-pd-1-pd-l1-on-nk-cells-and-monocyte-macrophages-is-more-prominent-in-hodgkin-lymphoma-than-dlbcl
#3
Frank Vari, David Arpon, Colm Keane, Mark S Hertzberg, Dipti Talaulikar, Sanjiv Jain, Qingyan Cui, Erica Han, Josh Tobin, Robert Bird, Donna Cross, Annette Hernandez, Clare Gould, Simone Birch, Maher K Gandhi
Much focus has been on the interaction of PD-L1 on malignant B-cells with PD-1 on effector T-cells in inhibiting anti-lymphoma immunity. We sought to establish the contribution of NK-cells and inhibitory CD163 + monocytes/macrophages in Hodgkin Lymphoma (cHL) and Diffuse Large B-cell Lymphoma (DLBCL). Levels of PD-1 on NK-cells were elevated in cHL relative to DLBCL. Notably, CD3 - CD56 hi CD16 -ve NK-cells had substantially higher PD-1 expression relative to CD3 - CD56 dim CD16 + cells, and were expanded in blood and tissue, more marked in cHL than DLBCL patients...
February 15, 2018: Blood
https://www.readbyqxmd.com/read/29448937/engineering-chimeric-antigen-receptor-t-cells-for-cancer-treatment
#4
REVIEW
Baixin Ye, Creed M Stary, Xuejun Li, Qingping Gao, Chunsheng Kang, Xiaoxing Xiong
Intratumor heterogeneity of tumor clones and an immunosuppressive microenvironment in cancer ecosystems contribute to inherent difficulties for tumor treatment. Recently, chimeric antigen receptor (CAR) T-cell therapy has been successfully applied in the treatment of B-cell malignancies, underscoring its great potential in antitumor therapy. However, functional challenges of CAR-T cell therapy, especially in solid tumors, remain. Here, we describe cancer-immunity phenotypes from a clonal-stromal-immune perspective and elucidate mechanisms of T-cell exhaustion that contribute to tumor immune evasion...
February 15, 2018: Molecular Cancer
https://www.readbyqxmd.com/read/29445583/deep-sustained-response-to-daratumumab-monotherapy-associated-with-t-cell-expansion-in-triple-refractory-myeloma
#5
Saad Z Usmani, Imran Khan, Christopher Chiu, David Foureau, Lawrence J Druhan, Katherine Rigby, Tineke Casneuf, A Kate Sasser
Background: Daratumumab, a human CD38 monoclonal antibody that has direct on-tumor and immunomodulatory mechanisms of action, demonstrated clinical benefit as monotherapy or in combination with established regimens in patients with multiple myeloma with one or more prior lines of therapy. Case presentation: A male patient, who was 70 years of age at the time of diagnosis of multiple myeloma in 2011, relapsed after five lines of therapy, including autologous stem cell transplantation...
2018: Experimental Hematology & Oncology
https://www.readbyqxmd.com/read/29444930/immunophenotyping-of-newly-diagnosed-and-recurrent-glioblastoma-defines-distinct-immune-exhaustion-profiles-in-peripheral-and-tumor-infiltrating-lymphocytes
#6
Malte Mohme, Simon Schliffke, Cecile L Maire, Alessandra Rünger, Laura Glau, Klaus C Mende, Jakob Matschke, Christina Gehbauer, Nuray Akyüz, Svenja Zapf, Mareike Holz, Miriam Schaper, Tobias Martens, Nils O Schmidt, Sven Peine, Manfred Westphal, Mascha Binder, Eva Tolosa, Katrin Lamszus
PURPOSE: Immunotherapeutic treatment strategies for glioblastoma (GBM) are under investigation in clinical trials. However, our understanding of the immune phenotype of GBM-infiltrating T-cells (TILs) and changes during disease progression is limited. Deeper insight is urgently needed to therapeutically overcome tumor-induced immune exhaustion. EXPERIMENTAL DESIGN: We used flow-cytometry and cytokine assays to profile TILs and blood lymphocytes (PBL) from GBM patients, comparing newly diagnosed or recurrent GBM to long-term survivors (LTS) and healthy donors...
February 14, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29444704/hpmsc-transplantation-restoring-ovarian-function-in-premature-ovarian-failure-mice-is-associated-with-change-of-th17-tc17-and-th17-treg-cell-ratios-through-the-pi3k-akt-signal-pathway
#7
Na Yin, Yanlin Wang, Xueyan Lu, Ranran Liu, Lianshuang Zhang, Wei Zhao, Wendan Yuan, Qianqian Luo, Hao Wu, Xiying Luan, Hongqin Zhang
BACKGROUND: Human placenta-derived mesenchymal stem cell (hPMSC) transplantation has been demonstrated to be an effective way of recovering ovarian function in mice with autoimmune induced premature ovarian failure (POF). But the exact mechanism remains unclear. The goal of the present study is to investigate the role of immune factors (T-helper 17 (Th17), cytotoxic T (Tc17) and regulatory T (Treg) cells) in the recovery of ovarian function and whether the phosphatidylinositol 3-kinase (PI3K)/Akt signal pathway is involved in the regulation...
February 14, 2018: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/29444087/safety-and-efficacy-of-anti-pd-l1-therapy-in-the-woodchuck-model-of-hbv-infection
#8
Scott Balsitis, Volodymyr Gali, Pamela J Mason, Susan Chaniewski, Steven M Levine, Michael J Wichroski, Michael Feulner, Yunling Song, Karen Granaldi, James K Loy, Chris M Thompson, Jacob A Lesniak, Catherine Brockus, Narendra Kishnani, Stephan Menne, Mark I Cockett, Renuka Iyer, Stephen W Mason, Daniel J Tenney
Immune clearance of Hepatitis B virus (HBV) is characterized by broad and robust antiviral T cell responses, while virus-specific T cells in chronic hepatitis B (CHB) are rare and exhibit immune exhaustion that includes programmed-death-1 (PD-1) expression on virus-specific T cells. Thus, an immunotherapy able to expand and activate virus-specific T cells may have therapeutic benefit for CHB patients. Like HBV-infected patients, woodchucks infected with woodchuck hepatitis virus (WHV) can have increased hepatic expression of PD-1-ligand-1 (PD-L1), increased PD-1 on CD8+ T cells, and a limited number of virus-specific T cells with substantial individual variation in these parameters...
2018: PloS One
https://www.readbyqxmd.com/read/29437767/t-cell-exhaustion-signatures-vary-with-tumor-type-and-are-severe-in-glioblastoma
#9
Karolina Woroniecka, Pakawat Chongsathidkiet, Kristen E Rhodin, Hanna R Kemeny, Cosette A Dechant, Samuel H Farber, Aladine A Elsamadicy, Xiuyu Cui, Shohei Koyama, Christina C Jackson, Landon J Hansen, Tanner M Johanns, Luis Sanchez-Perez, Vidyalakshmi Chandramohan, Yen-Rei A Yu, Darell D Bigner, Amber J Giles, Patrick Healy, Glenn Dranoff, Kent J Weinhold, Gavin P Dunn, Peter E Fecci
PURPOSE: T cell dysfunction is a hallmark of GBM. While anergy and tolerance have been well characterized, T cell exhaustion remains relatively unexplored. Exhaustion, characterized in part by the upregulation of multiple immune checkpoints, is a known contributor to failures amidst immune checkpoint blockade, a strategy that has lacked success thus far in GBM. This study is among the first to examine, and credential as bona fide, exhaustion among T cells infiltrating human and murine GBM...
February 7, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29427415/ccr8-expression-defines-tissue-resident-memory-t-cells-in-human-skin
#10
Michelle L McCully, Kristin Ladell, Robert Andrews, Rhiannon E Jones, Kelly L Miners, Laureline Roger, Duncan M Baird, Mark J Cameron, Zita M Jessop, Iain S Whitaker, Eleri L Davies, David A Price, Bernhard Moser
Human skin harbors two major T cell compartments of equal size that are distinguished by expression of the chemokine receptor CCR8. In vitro studies have demonstrated that CCR8 expression is regulated by TCR engagement and the skin tissue microenvironment. To extend these observations, we examined the relationship between CCR8+ and CCR8- skin T cells in vivo. Phenotypic, functional, and transcriptomic analyses revealed that CCR8+ skin T cells bear all the hallmarks of resident memory T cells, including homeostatic proliferation in response to IL-7 and IL-15, surface expression of tissue localization (CD103) and retention (CD69) markers, low levels of inhibitory receptors (programmed cell death protein 1, Tim-3, LAG-3), and a lack of senescence markers (CD57, killer cell lectin-like receptor subfamily G member 1)...
February 2, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29422056/turning-the-tables-on-cytomegalovirus-targeting-viral-fc-receptors-by-cars-containing-mutated-ch2-ch3-igg-spacer-domains
#11
Julia Proff, Charlotte U Brey, Armin Ensser, Wolfgang Holter, Manfred Lehner
BACKGROUND: During infection with human cytomegalovirus (HCMV) several viral proteins occur on cell surfaces in high quantity. We thus pursue an HLA-independent approach for immunotherapy of HCMV using chimeric antigen receptors (CARs) and bispecific BiTE® antibody constructs. In this context, HCMV-encoded proteins that mediate viral immune evasion and bind human IgG might represent particularly attractive target antigens. Unlike in observations of similar approaches for HIV and hepatitis B and C viruses, however, HCMV-infected cells develop a striking resistance to cytotoxic effector functions at later stages of the replication cycle...
February 8, 2018: Journal of Translational Medicine
https://www.readbyqxmd.com/read/29421624/comprehensive-overview-of-murine-epididymal-mononuclear-phagocytes-and-lymphocytes-unexpected-populations-arise
#12
Allison Voisin, Marjorie Whitfield, Christelle Damon-Soubeyrand, Chantal Goubely, Joëlle Henry-Berger, Fabrice Saez, Ayhan Kocer, Joël R Drevet, Rachel Guiton
Despite increasing evidence that epididymal immune disorders can lead to infertility, the cells and mechanisms underlying epididymal immunity remain poorly understood. In this study, we propose a rather exhaustive overview of innate and adaptive immune cells present in the murine caput and cauda epididymis. Using flow cytometry and a wide set of markers, we screened the broadest panel of immune cells ever, in this organ. For the first time, we unequivocally quantified the innate populations of monocytes, macrophages, and dendritic cells subtypes...
January 31, 2018: Journal of Reproductive Immunology
https://www.readbyqxmd.com/read/29415983/14-3-3%C3%AE-delivered-by-hepatocellular-carcinoma-derived-exosomes-impaired-anti-tumor-function-of-tumor-infiltrating-t%C3%A2-lymphocytes
#13
Xiaochen Wang, Haiyuan Shen, Guangyan Zhangyuan, Ruyi Huang, Wenjie Zhang, Qifeng He, Kangpeng Jin, Han Zhuo, Zechuan Zhang, Jincheng Wang, Beicheng Sun, Xiaojie Lu
Increasing evidence shows that the anti-tumor functions of tumor-infiltrating T lymphocytes (TILs) were inhibited significantly, but the underlying mechanisms remain not fully understood. In this study, we found that 14-3-3ζ expression was up-regulated in hepatocellular carcinoma (HCC) cells and in TILs. TILs with 14-3-3ζ high-expression (14-3-3ζhigh) exhibited impaired activation (CD69), proliferation (Ki67) and anti-tumor functions compared to 14-3-3ζ low expression (14-3-3ζlow) TILs. Flow cytometry assay showed that compared with 14-3-3ζlow CD8+T cells, 14-3-3ζhigh ones exhibited higher frequency of exhausted phenotypes as measured by inhibitory receptors such as PD-1, TIM-3, LAG3, and CTLA-4...
February 7, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29414259/cd8-t-cell-exhaustion-in-chronic-infection-and-cancer-opportunities-for-interventions
#14
Masao Hashimoto, Alice O Kamphorst, Se Jin Im, Haydn T Kissick, Rathi N Pillai, Suresh S Ramalingam, Koichi Araki, Rafi Ahmed
Antigen-specific CD8 T cells are central to the control of chronic infections and cancer, but persistent antigen stimulation results in T cell exhaustion. Exhausted CD8 T cells have decreased effector function and proliferative capacity, partly caused by overexpression of inhibitory receptors such as programmed cell death (PD)-1. Blockade of the PD-1 pathway has opened a new therapeutic avenue for reinvigorating T cell responses, with positive outcomes especially for patients with cancer. Other strategies to restore function in exhausted CD8 T cells are currently under evaluation-many in combination with PD-1-targeted therapy...
January 29, 2018: Annual Review of Medicine
https://www.readbyqxmd.com/read/29414066/strategies-to-overcome-hbv-specific-t-cell-exhaustion-checkpoint-inhibitors-and-metabolic-re-programming
#15
REVIEW
Paola Fisicaro, Carolina Boni, Valeria Barili, Diletta Laccabue, Carlo Ferrari
HBV-specific T cells play a key role in antiviral protection and failure to control HBV is associated with severely dysfunctional T cell responses. Therefore, functional T cell reconstitution represents a potential way to treat chronically infected patients. The growing understanding of the dysregulated transcriptional/epigenetic and metabolic programs underlying T cell exhaustion allows to envisage functional T cell reconstitution strategies based on the combined/sequential use of compounds able to induce decline of antigen load, checkpoint modulation, metabolic and epigenetic reprogramming with possible boosting of functionally restored responses by specific vaccines...
January 29, 2018: Current Opinion in Virology
https://www.readbyqxmd.com/read/29413757/dendritic-cells-pulsed-with-exosomes-in-combination-with-pd-1-antibody-increase-the-efficacy-of-sorafenib-in-hepatocellular-carcinoma-model
#16
Shengbin Shi, Quan Rao, Chuangnian Zhang, Xiuyuan Zhang, Yibo Qin, Zuoxing Niu
Advanced hepatocellular carcinoma (HCC) has limited therapeutic options. Immunotherapy is a promising treatment, while sorafenib is a first-line drug-based treatment for advanced HCC. However, the efficacy of sorafenib and immunotherapy in combination, have not been clearly evaluated. Sorafenib treatment has been shown to promote immunosuppression by increasing hypoxia in orthotopic HCC models. Here, we found that sorafenib treatment in mice with orthotopic HCC increased the expression of inhibitor programmed death-ligand 1 (PD-L1) and T-regulatory cells in tumor tissues...
January 27, 2018: Translational Oncology
https://www.readbyqxmd.com/read/29410671/age-dependent-pre-vaccination-immunity-affects-the-immunogenicity-of-varicella-zoster-vaccination-in-middle-aged-adults
#17
Marieke van der Heiden, Lia G H de Rond, Menno C van Zelm, Guy A M Berbers, Annemieke M H Boots, Anne-Marie Buisman
Background: Prevention of infectious diseases is of high priority in the rapidly aging population. Unfortunately, vaccine responses in the elderly are frequently diminished. Timely vaccination of middle-aged adults might improve the immune responses to vaccines, although knowledge on pathogen-specific immune responses and factors affecting these responses, in middle-aged adults is currently limited. We thus investigated the immune responses after vaccination with Zostavax consisting of live-attenuated varicella zoster virus (VZV)...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29409843/t-cell-dysfunction-and-patient-age-are-associated-with-poor-outcomes-after-mechanical-circulatory-support-device-implantation
#18
Joanna M Schaenman, Maura Rossetti, Yael Korin, Tiffany Sidwell, Victoria Groysberg, Emily Liang, Sitaram Vangala, Nicholas Wisniewski, Eleanor Chang, Maral Bakir, Galyna Bondar, Martin Cadeiras, Murray Kwon, Elaine F Reed, Mario Deng
Immunologic impairment may contribute to poor outcomes after implantation of mechanical circulatory support device (MCSD), with infection often as a terminal event. The study of immune dysfunction is of special relevance given the growing numbers of older patients with heart disease. The aim of the study was to define which immunologic characteristics are associated with development of adverse clinical outcomes after MCSD implantation. We isolated peripheral blood mononuclear cells (PBMC) from patients pre- and up to 20 days post-MCSD implantation and analyzed them by multiparameter flow cytometry for T cell dysfunction, including terminal differentiation, exhaustion, and senescence...
January 31, 2018: Human Immunology
https://www.readbyqxmd.com/read/29409351/cd33-specific-chimeric-antigen-receptor-t-cells-with-different-costimulators-showed-potent-anti-leukemia-efficacy-and-different-phenotype
#19
Saisai Li, Zhongfei Tao, Yingxi Xu, Jia Liu, Na An, Ying Wang, Haiyan Xing, Zheng Tian, Kejing Tang, Xiaolong Liao, Qing Rao, Min Wang, Jianxiang Wang
Acute myeloid leukemia (AML) is a kind of a malignant hematologic tumor caused by uncontrolled repopulation of myeloid hematopoietic stem cells (HSCs). Current therapeutic effects for AML patients are unsatisfactory. Especially relapsed and refractory AML still have poor prognosis. T cell modified by chimeric antigen receptor (CAR) is an immunotherapeutic strategy for malignancies, which has a broad developing prospect. Most of AML cells overexpress the myeloid antigen CD33. Therefore, CD33-specific CAR-T cells with different costimulators (CD28, 4-1BB or both, referred to as CD33 28z...
February 6, 2018: Human Gene Therapy
https://www.readbyqxmd.com/read/29403500/human-immunodeficiency-virus-type-1-elite-controllers-maintain-low-co-expression-of-inhibitory-receptors-on-cd4-t-cells
#20
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
keyword
keyword
19053
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"