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https://www.readbyqxmd.com/read/29135922/targeting-immune-cell-checkpoints-during-sepsis
#1
REVIEW
Naeem K Patil, Yin Guo, Liming Luan, Edward R Sherwood
Immunosuppression is increasingly being recognized as one of the causes of increased morbidity and mortality during sepsis. Both innate and adaptive immune system dysfunction have been shown to cause an impaired ability to eradicate the primary infection and also lead to frequent occurrence of secondary opportunistic infections. Pre-clinical and clinical studies have shown that inhibitory immune checkpoint molecules, including programmed death-1 (PD-1), programmed death ligand-1 (PD-L1), cytotoxic T lymphocyte antigen-4 (CTLA-4), T cell membrane protein-3 (TIM-3), Lymphocyte activation-gene-3 (LAG-3) and 2B4, are upregulated during the course of sepsis...
November 14, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29110713/temporal-and-spatial-distribution-of-lumpy-skin-disease-outbreaks-in-ethiopia-in-the-period-2000-to-2015
#2
W Molla, M C M de Jong, K Frankena
BACKGROUND: Lumpy skin disease (LSD) is an infectious viral disease of cattle caused by a virus of the genus Capripoxvirus. LSD was reported for the first time in Ethiopia in 1981 and subsequently became endemic. This time series study was undertaken with the aims of identifying the spatial and temporal distribution of LSD outbreaks and to forecast the future pattern of LSD outbreaks in Ethiopia. RESULTS: A total of 3811 LSD outbreaks were reported in Ethiopia between 2000 and 2015...
November 6, 2017: BMC Veterinary Research
https://www.readbyqxmd.com/read/29092013/lag-3-another-brake-to-release-in-breast-cancer
#3
M Kok
No abstract text is available yet for this article.
October 30, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/29080013/meta-analytic-evaluation-of-the-association-between-head-injury-and-risk-of-amyotrophic-lateral-sclerosis
#4
Yukari Watanabe, Takamitsu Watanabe
Head injury is considered as a potential risk factor for amyotrophic lateral sclerosis (ALS). However, several recent studies have suggested that head injury is not a cause, but a consequence of latent ALS. We aimed to evaluate such a possibility of reverse causation with meta-analyses considering time lags between the incidence of head injuries and the occurrence of ALS. We searched Medline and Web of Science for case-control, cross-sectional, or cohort studies that quantitatively investigated the head-injury-related risk of ALS and were published until 1 December 2016...
October 2017: European Journal of Epidemiology
https://www.readbyqxmd.com/read/29069302/mechanistic-overview-of-immune-checkpoints-to-support-the-rational-design-of-their-combinations-in-cancer-immunotherapy
#5
A Rotte, J Y Jin, V Lemaire
Checkpoint receptor blockers, known to act by blocking the pathways that inhibit immune cell activation and stimulate immune responses against tumor cells, have been immensely successful in the treatment of cancer. Among several checkpoint receptors of immune cells, cytotoxic T-lymphocyte-associated protein-4 (CTLA-4), programmed cell death protein-1 (PD-1), T-cell immunoglobulin and ITIM domain (TIGIT), T-cell immunoglobulin-3 (TIM-3) and lymphocyte activation gene 3 (LAG-3) are the most commonly targeted checkpoints for cancer immunotherapy...
October 24, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/29058578/temporal-dynamic-of-malaria-in-a-suburban-area-along-the-niger-river
#6
Mahamadou Soumana Sissoko, Kourane Sissoko, Bourama Kamate, Yacouba Samake, Siaka Goita, Abdoulaye Dabo, Mama Yena, Nadine Dessay, Renaud Piarroux, Ogobara K Doumbo, Jean Gaudart
BACKGROUND: Even if rainfall and temperature are factors classically associated to malaria, little is known about other meteorological factors, their variability and combinations related to malaria, in association with river height variations. Furthermore, in suburban area, urbanization and growing population density should be assessed in relation to these environmental factors. The aim of this study was to assess the impact of combined environmental, meteorological and hydrological factors on malaria incidence through time in the context of urbanization...
October 23, 2017: Malaria Journal
https://www.readbyqxmd.com/read/29045526/lag-3-tumor-infiltrating-lymphocytes-in-breast-cancer-clinical-correlates-and-association-with-pd-1-pd-l1-tumors
#7
S Burugu, D Gao, S Leung, S K Chia, T O Nielsen
BACKGROUND: Novel immune checkpoint blockade strategies are being evaluated in clinical trials and include targeting the lymphocyte activation gene 3 (LAG-3) checkpoint, alone or in combination with PD-1/PD-L1 blockade. We investigated LAG-3 expression and its prognostic value in a large series of breast cancer patients, and correlated LAG-3 expression with key biomarkers including PD-1 and PD-L1. EXPERIMENTAL DESIGN: LAG-3 expression was evaluated by immunohistochemistry (IHC) on two tissue microarray series incorporating 4322 breast cancer primary excision specimens (N=330 in the training and N= 3,992 in the validation set) linked to detailed clinico-pathological, biomarker and long term clinical outcome data...
September 25, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/29042417/restoration-of-natural-killer-cell-anti-metastatic-activity-by-il-12-and-checkpoint-blockade
#8
Isabel Ohs, Laura Ducimetiere, Joana Marinho, Paulina Kulig, Burkhard Becher, Sonia Tugues
Immune checkpoint therapies target tumor antigen-specific T cells, but less is known about their effects on natural killer (NK) cells, which help control metastasis. In studying the development of lung metastases, we found that NK cells lose their cytotoxic capacity and acquire a molecular signature defined by the expression of co-inhibitory receptors. In an effort to overcome this suppressive mechanism, we evaluated NK cell responses to the immunostimulatory cytokine IL-12. Exposure to IL-12 rescued the cytotoxicity of NK cells but also led to the emergence of an immature NK cell population which expressed high levels of the co-inhibitory molecules PD-1, Lag-3 and TIGIT, thereby limiting NK cell-mediated control of pulmonary metastases...
October 17, 2017: Cancer Research
https://www.readbyqxmd.com/read/29016879/agonist-ox40-immunotherapy-improves-survival-in-glioma-bearing-mice-and-is-complementary-with-vaccination-with-irradiated-gm-csf-expressing-tumor-cells
#9
Nusrat Jahan, Hammad Talat, William T Curry
Background: Glioma immunotherapy is an active area of clinical investigation. Glioma-associated immunosuppression remains an obstacle to efficacious immunotherapy, and combination approaches are likely necessary for durable success. OX40 is a member of the tumor necrosis factor receptor superfamily that is upregulated on activated lymphocytes, ligation of which results in enhanced activity and may be active against cancer. We sought to confirm the efficacy of agonist anti-OX40 immunotherapy against glioma and hypothesized that it is complementary with irradiated whole tumor cell vaccination...
July 7, 2017: Neuro-oncology
https://www.readbyqxmd.com/read/28987965/emerging-targets-in-cancer-immunotherapy
#10
REVIEW
Samantha Burugu, Amanda R Dancsok, Torsten O Nielsen
The first generation of immune checkpoint inhibitors (anti-CTLA-4 and anti-PD-1/PD-L1) targeted natural immune homeostasis pathways, co-opted by cancers, to drive anti-tumor immune responses. These agents led to unprecedented results in patients with previously incurable metastatic disease and may become first-line therapies for some advanced cancers. However, these agents are efficacious in only a minority of patients. Newer strategies are becoming available that target additional immunomodulatory mechanisms to activate patients' own anti-tumor immune responses...
October 5, 2017: Seminars in Cancer Biology
https://www.readbyqxmd.com/read/28977875/expression-of-lag-3-defines-exhaustion-of-intratumoral-pd-1-t-cells-and-correlates-with-poor-outcome-in-follicular-lymphoma
#11
Zhi-Zhang Yang, Hyo Jin Kim, Jose C Villasboas, Ya-Ping Chen, Tammy Price-Troska, Shahrzad Jalali, Mara Wilson, Anne J Novak, Stephen M Ansell
Exhausted T-cells in follicular lymphoma (FL) typically express PD-1, but expression of PD-1 is not limited to exhausted cells. Although expected to be functionally suppressed, we found that the population of intratumoral PD-1(+) T cells were predominantly responsible for production of cytokines and granules. This surprising finding prompted us to explore the involvement of LAG-3 to specifically identify functionally exhausted T cells. We found that LAG-3 was expressed on a subset of intratumoral T cells from FL and LAG-3(+) T cells almost exclusively came from PD-1(+) population...
September 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28947968/characterization-of-infiltrating-lymphocytes-in-human-benign-and-malignant-prostate-tissue
#12
Emelie Rådestad, Lars Egevad, Carl Jorns, Jonas Mattsson, Berit Sundberg, Silvia Nava, Bo-Göran Ericzon, Lars Henningsohn, Victor Levitsky, Michael Uhlin
Immune checkpoint blockade has shown promising results in numerous cancer types. However, in prostate cancer (PC), absent or limited responses have been reported. To investigate further, we compared the phenotype of infiltrating T-cells isolated from prostate tissue from patients with PC (n = 5), benign prostatic hyperplasia (BPH) (n = 27), BPH with concurrent PC (n = 4) and controls (n = 7). The majority of T-cells were CD8(+) and had a CCR7(-)CD45RO(+) effector memory phenotype. However, the yield of T-cells isolated from PC lesions was on average 20-fold higher than that obtained from control prostates...
September 1, 2017: Oncotarget
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
#13
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...
November 1, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28929191/overview-of-lag-3-expressing-il-10-producing-regulatory-t-cells
#14
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/28928158/characterization-of-the-immune-microenvironment-in-hepatocellular-carcinoma-hcc
#15
Mark Yarchoan, Dongmei Xing, Lan Luan, Haiying Xu, Rajni Sharma, Aleksandra Popovic, Timothy M Pawlik, Amy K Kim, Qingfeng Zhu, Elizabeth M Jaffee, Janis Taube, Robert A Anders
PURPOSE: Hepatocellular carcinoma (HCC) often arises in the setting of chronic liver inflammation and may be responsive to novel immunotherapies. EXPERIMENTAL DESIGN: To characterize the immune microenvironment in HCC, immunohistochemical (IHC) staining was performed for CD8 positive T lymphocytes, PD-1 positive and LAG-3 positive lymphocytes, CD163 positive macrophages, and PD-L1 expression in tumor and liver background from 29 cases of resected HCC. RESULTS: Expression of CD8 was reduced in tumor and expression of CD163 was reduced at the tumor interface...
September 19, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28912398/-therapeutic-cancer-vaccine-and-immune-checkpoint-inhibitor
#16
Kousaku Mimura, Koji Kono
Therapeutic cancer vaccine enhances a specific immune response against tumor cells in vivo, resulting in exertion of antitumor effects. On the other hand, immune checkpoint inhibitors promote the induction of tumor-specific T cells and also enhance the cytotoxic abilityof these T cells in tumor microenvironment. There is a possibilitythat immune checkpoint inhibitors enhance tumor immune responses induced bytherapeutic cancer vaccine, and it is expected that additive or synergistic effects will be obtained bythe combination of them...
September 2017: Gan to Kagaku Ryoho. Cancer & Chemotherapy
https://www.readbyqxmd.com/read/28904197/differential-inhibitory-receptor-expression-on-t-cells-delineates-functional-capacities-in-chronic-viral-infection
#17
Jeffrey E Teigler, Gennadiy Zelinskyy, Michael A Eller, Diane L Bolton, Mary Marovich, Alexander D Gordon, Aljawharah Alrubayyi, Galit Alter, Merlin L Robb, Jeffrey N Martin, Steven G Deeks, Nelson L Michael, Ulf Dittmer, Hendrik Streeck
Inhibitory receptors have been extensively described for their importance in regulating immune responses in chronic infections and cancers. Blocking the function of inhibitory receptors such as PD-1, CTLA-4, 2B4, Tim-3, and LAG-3 has shown promise for augmenting CD8 T cell activity and boosting pathogen-specific immunity. However, the prevalence of inhibitory receptors on CD4 T cells and their relative influence on CD4 T cell functionality in chronic HIV infection remains poorly described. We therefore determined and compared inhibitory receptor expression patterns of 2B4, CTLA-4, LAG-3, PD-1, and Tim-3 on virus-specific CD4 and CD8 T cells in relation to their functional T cell profile...
December 1, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28901003/expression-of-tim-3-and-lag-3-in-extranodal-nk-t-cell-lymphoma-nasal-type
#18
Yuhua Feng, Meizuo Zhong, Yiping Liu, Leyuan Wang, Youhong Tang
OBJECTIVE: To investigate the expression of TIM-3 and LAG-3 in extranodal NK/T cell lymphoma, nasal type (ENKTL), and evaluate the clinical and prognostic significance of TIM-3 and LAG-3 in ENKTL. METHODS: A total of 61 human paraffin-embedded specimens including 41 ENKTL and 20 rhinitis were involved. We performed immunohistochemistry to detect the expression of TIM-3 and LAG-3. We analyzed correlation between expression of TIM-3 and LAG-3 and clinicopathological features of ENKTL...
September 13, 2017: Histology and Histopathology
https://www.readbyqxmd.com/read/28900677/tim-3-lag-3-and-tigit
#19
Nicole Joller, Vijay K Kuchroo
Co-inhibitory receptors play a key role in regulating T cell responses and maintaining immune homeostasis. Their inhibitory function prevents autoimmune responses but also restricts the ability of T cells to mount effective immune responses against tumors or persistent pathogens. T cells express a module of co-inhibitory receptors, which display great diversity in expression, structure, and function. Here, we focus on the co-inhibitory receptors Tim-3, Lag-3, and TIGIT and how they regulate T cell function, maintenance of self-tolerance, their role in regulating ongoing T cell responses at peripheral tissues, and their synergistic effects in regulating autoimmunity and antitumor responses...
September 13, 2017: Current Topics in Microbiology and Immunology
https://www.readbyqxmd.com/read/28899396/transcriptomic-meta-analysis-identifies-gene-expression-characteristics-in-various-samples-of-hiv-infected-patients-with-nonprogressive-disease
#20
Le-Le Zhang, Zi-Ning Zhang, Xian Wu, Yong-Jun Jiang, Ya-Jing Fu, Hong Shang
BACKGROUND: A small proportion of HIV-infected patients remain clinically and/or immunologically stable for years, including elite controllers (ECs) who have undetectable viremia (<50 copies/ml) and long-term nonprogressors (LTNPs) who maintain normal CD4(+) T cell counts for prolonged periods (>10 years). However, the mechanism of nonprogression needs to be further resolved. In this study, a transcriptome meta-analysis was performed on nonprogressor and progressor microarray data to identify differential transcriptome pathways and potential biomarkers...
September 12, 2017: Journal of Translational Medicine
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