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T cell exhaustion

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https://www.readbyqxmd.com/read/29142466/higher-pd-1-expression-concurrent-with-exhausted-cd8-t-cells-in-patients-with-de-novo-acute-myeloid-leukemia
#1
Jiaxiong Tan, Shaohua Chen, Yuhong Lu, Danlin Yao, Ling Xu, Yikai Zhang, Lijian Yang, Jie Chen, Jing Lai, Zhi Yu, Kanger Zhu, Yangqiu Li
Objective: To investigate the association between the T cell inhibitory receptor programmed death 1 (PD-1) and T cell exhaustion status in T cells from patients with de novo acute myeloid leukemia (AML) and AML in complete remission (CR). Methods: Surface expression of PD-1 and the exhaustion and immunosenescence markers CD244 and CD57 on CD3+, CD4+ and CD8+ T cells from peripheral blood samples from 20 newly diagnosed, untreated AML patients and 10 cases with AML in CR was analyzed by flow cytometry...
October 2017: Chinese Journal of Cancer Research, Chung-kuo Yen Cheng Yen Chiu
https://www.readbyqxmd.com/read/29141882/transparent-anemone-shrimp-ancylomenes-pedersoni-become-opaque-after-exercise-and-physiological-stress-in-correlation-with-increased-hemolymph-perfusion
#2
Laura E Bagge, Stephen T Kinsey, Justin Gladman, Sönke Johnsen
Whole-body transparency, an effective camouflage strategy in many aquatic species, can be disrupted by environmental and/or physiological stressors. We found that tail-flip escape responses temporarily disrupt the transparency of the anemone shrimp Ancylomenes pedersoni After as few as three tail flips, the previously transparent abdominal muscle became cloudy. Eliciting additional tail flips to the point of exhaustion (16±1 s.e.m.; n=23) resulted in complete opacity, though the original transparency returned after 20-60 min of inactivity...
November 15, 2017: Journal of Experimental Biology
https://www.readbyqxmd.com/read/29140111/purging-exhausted-virus-specific-cd8-t-cell-phenotypes-by-somatic-cell-reprogramming
#3
Joshua Chan, Patrick Y Kim, Emiko Kranz, Yoshiko Nagaoka, YooJin Lee, Jing Wen, Heidi J Elsaesser, Meng Qin, David G Brooks, Gene-Errol Ringpis, Irvin S Y Chen, Masakazu Kamata
Cytotoxic T cells are critical in controlling virus infections. However, continuous antigen stimulation and negative regulatory factors cause CD8 T cells to enter a dysfunctional state (T cell exhaustion), resulting in viral persistence. We hypothesized that the exhausted T cell state could be molecularly rejuvenated using a somatic cell reprogramming technology, which is technically able to convert any types of cells to induced pluripotent stem cells (iPSCs), to regenerate functional T cells capable of purging chronic infection...
November 2017: AIDS Research and Human Retroviruses
https://www.readbyqxmd.com/read/29137886/diesel-exhaust-inhalation-exposure-induces-pulmonary-arterial-hypertension-in-mice
#4
Jing Liu, Xiaoqing Ye, Dapeng Ji, Xiaofei Zhou, Cong Qiu, Weiping Liu, Luyang Yu
Diesel exhaust (DE) is one of the main sources of urban air pollution. An increasing number of evidence showed the association of air pollution with cardiovascular diseases. Pulmonary arterial hypertension (PAH) is one of the most disastrous vascular diseases, which results in right ventricular failure and death. However, the relationship of DE inhalation exposure with PAH is still unknown. In this study, male adult mice were exposed by inhalation to filtered ambient air (negative control), 10% O2 hypoxia (PAH-phenotype positive control), 350 μg/m(3) particulate matter whole DE, or the combination of DE and hypoxic condition...
November 11, 2017: Environmental Pollution
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
#5
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/29137227/re-balance-of-memory-t-cell-subsets-in-peripheral-blood-from-patients-with-cml-after-tki-treatment
#6
Danlin Yao, Ling Xu, Jiaxiong Tan, Yikai Zhang, Shuai Lu, Mingde Li, Sichun Lu, Lijian Yang, Shaohua Chen, Jie Chen, Jing Lai, Yuhong Lu, Xiuli Wu, Xianfeng Zha, Yangqiu Li
T cell immune surveillance is considered an important host protection process for inhibiting carcinogenesis. The full capacity of T cell immune surveillance is dependent on T cell homeostasis, particularly for central memory T (TCM) cells and stem cell memory T (TSCM) cells. In this study, distribution of T cell subsets in peripheral blood from 12 patients with chronic myeloid leukemia (CML) and 12 cases with CML in complete remission (CR) was analyzed using a multicolor flow cytometer, and 16 samples from healthy individuals (HIs) served as control...
October 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29128997/pd-1-pd-l1-immune-checkpoint-blockade-in-malignant-lymphomas
#7
REVIEW
Yi Wang, Ling Wu, Chen Tian, Yizhuo Zhang
Tumor cells can evade immune surveillance through overexpressing the ligands of checkpoint receptors on tumor cells or adjacent cells, leading T cells to anergy or exhaustion. Growing evidence of the interaction between tumor cells and microenvironment promoted the emergence of immune-checkpoint blockade. By targeting programmed cell death-1 (PD-1) pathway, cytotoxic activity of T cell is enhanced significantly and tumor cell lysis is induced subsequently. Currently, various antibodies against PD-1 and programmed death-ligand 1 (PD-L1) are under clinical studies in lymphomas...
November 11, 2017: Annals of Hematology
https://www.readbyqxmd.com/read/29127145/tim-3-engagement-promotes-effector-memory-t-cell-differentiation-of-human-antigen-specific-cd8-t-cells-by-activating-mtorc1
#8
Nina Chi Sabins, Olesya Chornoguz, Karen Leander, Fred Kaplan, Richard Carter, Michelle Kinder, Kurtis Bachman, Raluca Verona, Shixue Shen, Vipul Bhargava, Sandra Santulli-Marotto
T cell expression of TIM-3 following Ag encounter has been associated with a continuum of functional states ranging from effector memory T cells to exhaustion. We have designed an in vitro culture system to specifically address the impact of anti-TIM-3/TIM-3 engagement on human Ag-specific CD8 T cells during a normal response to Ag and found that anti-TIM-3 treatment enhances T cell function. In our in vitro T cell culture system, MART1-specific CD8 T cells were expanded from healthy donors using artificial APCs...
November 10, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29123966/pd-1-blockade-at-the-time-of-tumor-escape-potentiates-the-immune-mediated-antitumor-effects-of-a-melanoma-targeting-monoclonal-antibody
#9
Laetitia They, Henri-Alexandre Michaud, Ondine Becquart, Virginie Lafont, Bernard Guillot, Florence Boissière-Michot, Marta Jarlier, Caroline Mollevi, Jean-François Eliaou, Nathalie Bonnefoy, Laurent Gros
Tumor antigen-targeting monoclonal antibodies (TA-targeting mAbs) are used as therapeutics in many malignancies and their capacity to mobilize the host immunity puts them at the forefront of anti-cancer immunotherapies. Both innate and adaptive immune cells have been associated with the therapeutic activity of such antibodies, but tumor escape from mAb-induced tumor immune surveillance remains one of the main clinical issues. In this preclinical study, we grafted immunocompetent and immunocompromised mice with the B16F10 mouse melanoma cell line and treated them with the TA99 TA-targeting mAb to analyze the immune mechanisms associated with the tumor response and resistance to TA99 monotherapy...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/29119407/pd-l1-testing-in-guiding-patient-selection-for-pd-1-pd-l1-inhibitor-therapy-in-lung-cancer
#10
Katerina Ancevski Hunter, Mark A Socinski, Liza C Villaruz
Immunotherapy with programmed death 1 (PD-1)- and programmed death-ligand 1 (PD-L1)-targeted monoclonal antibodies has dramatically changed the therapeutic and prognostic landscape for several types of malignancy. PD-1 and PD-L1 are immune checkpoint proteins whose binding ultimately result in T cell exhaustion and self-tolerance. Blocking this pathway 'releases the brakes' on the immune system and allows for attack of tumor cells that express PD-L1. The clinical trials that led to the US Food and Drug Administration (FDA) approval of these agents used different immunohistochemical (IHC) platforms with various PD-L1 antibodies to assess for PD-L1 expression on either tumor cells or tumor-infiltrating immune cells...
November 8, 2017: Molecular Diagnosis & Therapy
https://www.readbyqxmd.com/read/29118007/pd-1-expression-and-clinical-pd-1-blockade-in-b-cell-lymphomas
#11
Zijun Y Xu-Monette, Jianfeng Zhou, Ken H Young
PD-1 blockade targeting the PD-1 immune checkpoint has demonstrated unprecedented clinical efficacy in the treatment of advanced cancers including hematologic malignancies. This article reviews the landscape of PD-1/PD-L1 expression and current PD-1 blockade immunotherapy trials in B-cell lymphomas. Most notably, in relapsed/refractory classical Hodgkin lymphoma, which frequently has increased PD-1(+) tumor-infiltrating T cells, 9p24 genetic alteration and high PD-L1 expression, anti-PD-1 monotherapy has demonstrated remarkable objective response rates (ORR) of 65-87% and durable disease control in phase I/II clinical trials...
November 8, 2017: Blood
https://www.readbyqxmd.com/read/29115974/stat3-blocked-whole-cell-hepatoma-vaccine-induces-cellular-and-humoral-immune-response-against-hcc
#12
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
https://www.readbyqxmd.com/read/29113470/posttransplant-immune-activation-innocent-bystander-or-insidious-culprit-of-posttransplant-accelerated-atherosclerosis
#13
Didier Ducloux, Jamal Bamoulid, Thomas Crepin, Jean-Michel Rebibou, Cecile Courivaud, Philippe Saas
Cardiovascular disease is a major cause of morbidity, disability, and mortality in kidney transplant patients. Cumulative reports indicate that the excessive risk of cardiovascular events is not entirely explained by the increased prevalence of traditional cardiovascular risk factors. Atherosclerosis is a chronic inflammatory disease, and it has been postulated that posttransplant immune disturbances may explain the gap between the predicted and observed risks of cardiovascular events. Although concordant data suggest that innate immunity contributes to the posttransplant accelerated atherosclerosis, only few arguments plead for a role of adaptive immunity...
September 2017: Cell Transplantation
https://www.readbyqxmd.com/read/29109120/cd27-mediated-regulatory-t-cell-depletion-and-effector-t-cell-costimulation-both-contribute-to-antitumor-efficacy
#14
Anna Wasiuk, James Testa, Jeff Weidlick, Crystal Sisson, Laura Vitale, Jenifer Widger, Andrea Crocker, Lawrence J Thomas, Joel Goldstein, Henry C Marsh, Tibor Keler, Li-Zhen He
CD27, a member of the TNFR superfamily, is constitutively expressed in most T cells and plays crucial roles in T cell effector functions. The costimulation and antitumor activity of CD27 agonistic Abs have been well documented in mouse models. Clinical testing of a human IgG1 anti-CD27 Ab, varlilumab (clone 1F5), is ongoing in cancer patients. In this study, we set out to further understand CD27 as an immunomodulatory target and to address the mechanism of antitumor efficacy using different IgG isotypes of 1F5 in human CD27-transgenic mice...
November 6, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29105335/tetraselmis-suecica-f-m-m33-growth-is-influenced-by-its-associated-bacteria
#15
Natascia Biondi, Giulia Cheloni, Liliana Rodolfi, Carlo Viti, Luciana Giovannetti, Mario R Tredici
Algal cultures are usually co-cultures of algae and bacteria, especially when considering outdoor mass cultivation. The influence of associated bacteria on algal culture performance has been poorly investigated, although bacteria may strongly affect biomass (or derived product) yield and quality. In this work, the influence on growth and productivity of Tetraselmis suecica F&M-M33 of bacterial communities and single bacterial isolates from the algal phycosphere was investigated. Xenic laboratory and outdoor cultures were compared with an axenic culture in batch...
November 3, 2017: Microbial Biotechnology
https://www.readbyqxmd.com/read/29101105/cytokine-mediated-regulation-of-cd8-t-cell-responses-during-acute-and-chronic-viral-infection
#16
Masao Hashimoto, Se Jin Im, Koichi Araki, Rafi Ahmed
The common γ-chain cytokines, interleukin (IL)-2, IL-7, and IL-15, regulate critical aspects of antiviral CD8 T-cell responses. During acute infections, IL-2 controls expansion and differentiation of antiviral CD8 T cells, whereas IL-7 and IL-15 are key cytokines to maintain memory CD8 T cells long term in an antigen-independent manner. On the other hand, during chronic infections, in which T-cell exhaustion is established, precise roles of these cytokines in regulation of antiviral CD8 T-cell responses are not well defined...
November 3, 2017: Cold Spring Harbor Perspectives in Biology
https://www.readbyqxmd.com/read/29093707/add-on-pyridostigmine-enhances-cd4-t-cell-recovery-in-hiv-1-infected-immunological-non-responders-a-proof-of-concept-study
#17
Sergio I Valdés-Ferrer, José C Crispín, Pablo F Belaunzarán-Zamudio, Carlos A Rodríguez-Osorio, Bernardo Cacho-Díaz, Jorge Alcocer-Varela, Carlos Cantú-Brito, Juan Sierra-Madero
Background: In human immunodeficiency virus (HIV)-infection, persistent T-cell activation leads to rapid turnover and increased cell death, leading to immune exhaustion and increased susceptibility to opportunistic infections. Stimulation of the vagus nerve increases acetylcholine (ACh) release and modulates inflammation in chronic inflammatory conditions, a neural mechanism known as the cholinergic anti-inflammatory pathway (CAP). Pyridostigmine (PDG), an ACh-esterase inhibitor, increases the half-life of endogenous ACh, therefore mimicking the CAP...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29093082/according-to-hcv-infection-stage-il-7-plus-4-1bb-triggering-alone-or-combined-with-pd-1-blockade-increases-traf1-low-hcv-specific-cd8-cell-reactivity
#18
Elia Moreno-Cubero, Dolores Subirá, Eduardo Sanz-de-Villalobos, Trinidad Parra-Cid, Antonio Madejón, Joaquín Miquel, Antonio Olveira, Alejandro González-Praetorius, Javier García-Samaniego, Juan-Ramón Larrubia
Hepatitis C virus (HCV)-specific CD8(+) T cells suffer a progressive exhaustion during persistent HCV infection (PI). This process could involve the positive immune checkpoint 4-1BB/4-1BBL, through the loss of its signal transducer TRAF1. To address this issue, peripheral HCV-specific CD8(+) T cells (Pentamer(+)/CD8(+)) from patients with PI and resolved infection after treatment (RI) were studied. Duration of HCV infection and liver fibrosis progression rate inversely correlated with the likelihood of detecting peripheral pentamer(+)/CD8(+) cells...
November 1, 2017: Journal of Virology
https://www.readbyqxmd.com/read/29084057/evaluation-of-pd1-pdl1-expression-and-their-clinicopathologic-association-in-ebv-associated-lymphoproliferative-disorders-in-nonimmunosuppressed-patients
#19
Ling Guo, Juraj Bodo, Lisa Durkin, Eric D Hsi
Epstein-Barr virus (EBV)-associated lymphoproliferative disorders (LPD)/lymphomas in nonimmunosuppressed patients represent a unique entity and have been proposed to be related to immune senescence. Engagement of programmed cell death 1 (PD1) by its ligand programmed death ligand 1 (PDL1) inhibits T-cell activation, and leads to T-cell exhaustion. In clinical trials, therapeutic antibodies that block the PD1-PDL1 axis have shown promising therapeutic activity in certain types of lymphomas. Although PD1/PDL1 has been extensively studied in variety of lymphomas, there are few reports characterizing their expression in EBV-positive LPD...
October 27, 2017: Applied Immunohistochemistry & Molecular Morphology: AIMM
https://www.readbyqxmd.com/read/29083978/immunotherapy-regimens-for-metastatic-colorectal-carcinomas
#20
Babar Bashir, Adam E Snook
Metastatic colorectal cancer (mCRC) is a leading cause of cancer-related mortality with a 5-year overall survival rate of 13%. Despite recent advances in cancer immunotherapy, only the minority of CRC patients (<15%) with microsatellite instability can potentially benefit from immune checkpoint inhibitors, the only immunotherapy currently approved for mCRC. In that context, there is an unmet need to improve survival in mCRC. Our ever-increasing understanding of the immune system and its interactions with cancer has allowed development of multiple strategies to potentially improve outcomes in the majority of mCRC patients...
October 30, 2017: Human Vaccines & Immunotherapeutics
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