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https://www.readbyqxmd.com/read/29308304/pd-1-related-transcriptome-profile-and-clinical-outcome-in-diffuse-gliomas
#1
Shuai Liu, Zheng Wang, Yinyan Wang, Xing Fan, Chuanbao Zhang, Wenbin Ma, Xiaoguang Qiu, Tao Jiang
Background: PD-1 plays a critical part in control of immune response to malignancy. Anti-PD-1 treatment is a hopeful strategy to improve the dismal prognosis of gliomas. To characterize the role of PD-1 in diffuse gliomas, we investigated its related biological process at transcriptome level and its clinical prognostic value. Method and patients: Through Chinese Glioma Genome Atlas and TCGA datasets, we systematically reviewed a total of 994 cases with RNA-seq data and analyzed the functional annotation of PD-1 by Gene ontology (GO) analysis...
2018: Oncoimmunology
https://www.readbyqxmd.com/read/29259116/mixed-signature-of-activation-and-dysfunction-allows-human-decidual-cd8-t-cells-to-provide-both-tolerance-and-immunity
#2
Anita van der Zwan, Kevin Bi, Errol R Norwitz, Ângela C Crespo, Frans H J Claas, Jack L Strominger, Tamara Tilburgs
Understanding how decidual CD8+ T cell (CD8+ dT) cytotoxicity is regulated and how these cells integrate the competing needs for maternal-fetal tolerance and immunity to infection is an important research and clinical goal. Gene-expression analysis of effector-memory CD8+ dT demonstrated a mixed transcriptional signature of T cell dysfunction, activation, and effector function. High protein expression of coinhibitory molecules PD1, CTLA4, and LAG3, accompanied by low expression of cytolytic molecules suggests that the decidual microenvironment reduces CD8+ dT effector responses to maintain tolerance to fetal antigens...
December 19, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29209313/unconventional-pro-inflammatory-cd4-t-cell-response-in-b-cell-deficient-mice-infected-with-trypanosoma-cruzi
#3
Melisa Gorosito Serrán, Jimena Tosello Boari, Facundo Fiocca Vernengo, Cristian G Beccaría, María C Ramello, Daniela A Bermejo, Amelia G Cook, Carola G Vinuesa, Carolina L Montes, Eva V Acosta Rodriguez, Adriana Gruppi
Chagas disease, caused by the parasite Trypanosoma cruzi, is endemic in Latin America but has become a global public health concern by migration of infected people. It has been reported that parasite persistence as well as the intensity of the inflammatory immune response are determinants of the clinical manifestations of the disease. Even though inflammation is indispensable for host defense, when deregulated, it can contribute to tissue injury and organ dysfunction. Here, we report the importance of B cells in conditioning T cell response in T...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29163490/immune-checkpoint-molecules-on-tumor-infiltrating-lymphocytes-and-their-association-with-tertiary-lymphoid-structures-in-human-breast-cancer
#4
Cinzia Solinas, Soizic Garaud, Pushpamali De Silva, Anaïs Boisson, Gert Van den Eynden, Alexandre de Wind, Paolo Risso, Joel Rodrigues Vitória, François Richard, Edoardo Migliori, Grégory Noël, Hugues Duvillier, Ligia Craciun, Isabelle Veys, Ahmad Awada, Vincent Detours, Denis Larsimont, Martine Piccart-Gebhart, Karen Willard-Gallo
There is an exponentially growing interest in targeting immune checkpoint molecules in breast cancer (BC), particularly in the triple-negative subtype where unmet treatment needs remain. This study was designed to analyze the expression, localization, and prognostic role of PD-1, PD-L1, PD-L2, CTLA-4, LAG3, and TIM3 in primary BC. Gene expression analysis using the METABRIC microarray dataset found that all six immune checkpoint molecules are highly expressed in basal-like and HER2-enriched compared to the other BC molecular subtypes...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29151021/regulatory-t-cells-induced-by-b-cells-a-novel-subpopulation-of-regulatory-t-cells
#5
REVIEW
Chien-Hui Chien, Bor-Luen Chiang
Regulatory T cells play a crucial role in the homeostasis of the immune response. In addition to CD4+Foxp3+ regulatory T cells, several subsets of Foxp3- regulatory T cells, such as T helper 3 (Th3) cells and type 1 regulatory T (Tr1) cells, have been described in mice and human. Accumulating evidence shows that naïve B cells contribute to tolerance and are able to promote regulatory T cell differentiation. Naïve B cells can convert CD4+CD25- T cells into CD25+Foxp3- regulatory T cells, named Treg-of-B cells by our group...
November 18, 2017: Journal of Biomedical Science
https://www.readbyqxmd.com/read/29089645/identification-and-characterization-of-hla-a24-specific-xbp1-cd138-syndecan-1-and-cs1-slamf7-peptides-inducing-antigens-specific-memory-cytotoxic-t-lymphocytes-targeting-multiple-myeloma
#6
J Bae, T Hideshima, G L Zhang, J Zhou, D B Keskin, N C Munshi, K C Anderson
XBP1 (X-box binding protein 1), CD138 (Syndecan-1), and CS1 (SLAMF7) are highly expressed antigens in cancers including multiple myeloma (MM). Here we identify and characterize immunogenic HLA-A24 peptides derived from these antigens for potential vaccination therapy of HLA-A24+ patients with MM. The identified immunogenic HLA-A24-specific XBP1 unspliced (UN)185-193 (I S P W I L A V L), XBP1 spliced (SP)223-231 (V Y P E G P S S L), CD138265-273 (I F A V C L V G F) and CS1240-248 (L F V L G L F L W) peptides induced antigen-specific CTL with anti-MM activity in an HLA-A24 restricted manner...
November 1, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/29047105/%C3%AE-secretase-inhibitor-reduces-immunosuppressive-cells-and-enhances-tumour-immunity-in-head-and-neck-squamous-cell-carcinoma
#7
Liang Mao, Zhi-Li Zhao, Guang-Tao Yu, Lei Wu, Wei-Wei Deng, Yi-Cun Li, Jian-Feng Liu, Lin-Lin Bu, Bing Liu, Ashok B Kulkarni, Wen-Feng Zhang, Lu Zhang, Zhi-Jun Sun
Immune evasion is a hallmark feature of cancer, and it plays an important role in tumour initiation and progression. In addition, tumour immune evasion severely hampers the desired antitumour effect in multiple cancers. In this study, we aimed to investigate the role of the Notch pathway in immune evasion in the head and neck squamous cell carcinoma (HNSCC) microenvironment. We first demonstrated that Notch1 signalling was activated in a Tgfbr1/Pten-knockout HNSCC mouse model. Notch signalling inhibition using a γ-secretase inhibitor (GSI-IX, DAPT) decreased tumour burden in the mouse model after prophylactic treatment...
October 19, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28994421/breast-cancer-lag3-expression-indicates-favourable-outcomes
#8
Peter Sidaway
No abstract text is available yet for this article.
December 2017: Nature Reviews. Clinical Oncology
https://www.readbyqxmd.com/read/28982868/peripheral-tr1-and-foxp3-treg-as-markers-of-recurrent-malignancies-in-patients-with-hepato-biliary-pancreatic-cancers
#9
Tetsuya Ikemoto, Mitsuo Shimada, Daichi Ishikawa, Yoichiro Kawashita, Hiroki Teraoku, Masato Yoshikawa, Shinichiro Yamada, Y U Saito, Yuji Morine, Satoru Imura
BACKGROUND/AIM: Recently CD4(+)CD49b(+) LAG3(+)regulatory T (Tr1) cells are reported to be IL-10 driven, have strong regulatory activities. Thus, this study aimed to investigate whether Treg and Tr1 cells participate in immunological status against cancer. PATIENTS AND METHODS: Peripheral blood was withdrawn from patients (n=78), and healthy volunteers as controls (n=23). The peripheral blood mononuclear cells were subjected to FACScan analysis after labeling with anti-CD4, -CD25, - Foxp3, -CD49b and -LAG3 antibodies...
October 2017: Anticancer Research
https://www.readbyqxmd.com/read/28935468/function-and-regulation-of-lag3-on-cd4-cd25-t-cells-in-non-small-cell-lung-cancer
#10
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...
November 15, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28934318/identification-of-lag3-high-affinity-aptamers-by-ht-selex-and-conserved-motif-accumulation-cma
#11
Mario Martínez Soldevilla, Sandra Hervas, Helena Villanueva, Teresa Lozano, Obdulia Rabal, Julen Oyarzabal, Juan José Lasarte, Maurizio Bendandi, Susana Inoges, Ascensión López-Díaz de Cerio, Fernando Pastor
LAG3 receptor belongs to a family of immune-checkpoints expressed in T lymphocytes and other cells of the immune system. It plays an important role as a rheostat of the immune response. Focus on this receptor as a potential therapeutic target in cancer immunotherapy has been underscored after the success of other immune-checkpoint blockade strategies in clinical trials. LAG3 showcases the interest in the field of autoimmunity as several studies show that LAG3-targeting antibodies can also be used for the treatment of autoimmune diseases...
2017: PloS One
https://www.readbyqxmd.com/read/28929191/overview-of-lag-3-expressing-il-10-producing-regulatory-t-cells
#12
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/28921877/analysis-of-infantile-fibrosarcoma-reveals-extensive-t-cell-responses-within-tumors-implications-for-immunotherapy
#13
Hua Zhu, Song Gu, Minzhi Yin, Min Shi, Chao Xin, Jianmin Zhu, Jing Wang, Siqi Huang, Chenjie Xie, Jing Ma, Ci Pan, Jingyan Tang, Min Xu, Xue-Feng Bai
BACKGROUND: Infantile fibrosarcoma (IFS) is a rare pediatric malignancy with relatively good prognosis, but the risk of progression or recurrence after therapy exists. To understand the immune microenvironment of IFS and determine if immunotherapy is a potential treatment, we analyzed T-cell responses in IFS tumors. PROCEDURE: IFS tumors were analyzed by immunohistochemistry and multicolor flow cytometry to characterize immune cell infiltration and function. Tumor infiltrating lymphocytes (TILs) were expanded in vitro and evaluated for recognition of autologous tumor cells...
September 17, 2017: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/28920005/the-frequency-of-neoantigens-per-somatic-mutation-rather-than-overall-mutational-load-or-number-of-predicted-neoantigens-per-se-is-a-prognostic-factor-in-ovarian-clear-cell-carcinoma
#14
Hirokazu Matsushita, Kosei Hasegawa, Katsutoshi Oda, Shogo Yamamoto, Akira Nishijima, Yuichi Imai, Kayo Asada, Yuji Ikeda, Takahiro Karasaki, Keiichi Fujiwara, Hiroyuki Aburatani, Kazuhiro Kakimi
Neoantigens derived from tumor-specific somatic mutations are excellent targets for anti-tumor immune responses. In ovarian clear cell carcinoma (OCCC), checkpoint blockade yields durable responses in a subset of patients. To approach the question of why only some patients respond, we first investigated neoantigen loads and immune signatures using exome sequencing and expression array data for 74 OCCC patients treated conventionally. Neither the number of missense mutations nor total predicted neoantigens assessed in the tumor correlated with clinical outcomes...
2017: Oncoimmunology
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
#15
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/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...
November 15, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28833046/ahr-activation-increases-il-2-production-by-alloreactive-cd4-t-cells-initiating-the-differentiation-of-mucosal-homing-tim3-lag3-tr1-cells
#17
Allison K Ehrlich, Jamie M Pennington, Susan Tilton, Xisheng Wang, Nikki B Marshall, Diana Rohlman, Castle Funatake, Sumit Punj, Edmond O'Donnell, Zhen Yu, Siva K Kolluri, Nancy I Kerkvliet
Activation of the aryl hydrocarbon receptor (AhR) by immunosuppressive ligands promotes the development of regulatory T (Treg) cells. Although AhR-induced Foxp3(+) Treg cells have been well studied, much less is known about the development and fate of AhR-induced Type 1 Treg (AhR-Tr1) cells. In the current study, we identified the unique transcriptional and functional changes in murine CD4(+) T cells that accompany the differentiation of AhR-Tr1 cells during the CD4(+) T-cell-dependent phase of an allospecific cytotoxic T lymphocyte (allo-CTL) response...
November 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28814904/the-journey-of-rheumatoid-arthritis-patients-a-review-of-reported-lag-times-from-the-onset-of-symptoms
#18
REVIEW
Alaa S Barhamain, Rami F Magliah, Mohammad H Shaheen, Shurooq F Munassar, Ayman M Falemban, Mohammed M Alshareef, Hani M Almoallim
BACKGROUND: Even after achieving tremendous advances in diagnosis and treatment of rheumatoid arthritis (RA), many of the patients undergo delays in diagnosis and initiation of treatment, which leads to worsening of the condition and poor prognosis. OBJECTIVE: The objective of this study was to perform a literature review to quantify the lag times in diagnosis and treatment of RA and study the reported factors associated with it. METHODS: The authors searched literature published until September 2016 in electronic full-text and abstract databases and hand-searched the suitable articles...
2017: Open Access Rheumatology: Research and Reviews
https://www.readbyqxmd.com/read/28806299/the-dynamic-and-transient-immune-microenvironment-in-locally-advanced-esophageal-adenocarcinoma-post-chemoradiation
#19
Ronan J Kelly, Ali H Zaidi, Matthew A Smith, Ashten N Omstead, Juliann E Kosovec, Daisuke Matsui, Samantha A Martin, Christina DiCarlo, E Day Werts, Jan F Silverman, David H Wang, Blair A Jobe
OBJECTIVE: The aim of this study was to assess the impact of chemoradiation on the immune microenvironment to influence and optimally design future neoadjuvant clinical trials. SUMMARY BACKGROUND DATA: Programmed death (PD)-1 inhibitors in metastatic gastroesophageal cancer have demonstrated response rates of approximately 25% in programmed death ligand-1 (PD-L1+) tumors. Unfortunately, the majority of patients do not respond. Therefore, a rationale strategy of combining immunotherapeutic agents with chemoradiation in earlier stage esophageal cancer may prevent metastatic disease in patients...
August 10, 2017: Annals of Surgery
https://www.readbyqxmd.com/read/28783703/lag3-limits-regulatory-t-cell-proliferation-and-function-in-autoimmune-diabetes
#20
Qianxia Zhang, Maria Chikina, Andrea L Szymczak-Workman, William Horne, Jay K Kolls, Kate M Vignali, Daniel Normolle, Maria Bettini, Creg J Workman, Dario A A Vignali
Inhibitory receptors (IRs) are pivotal in controlling T cell homeostasis because of their intrinsic regulation of conventional effector T (Tconv) cell proliferation, viability, and function. However, the role of IRs on regulatory T cells (Tregs) remains obscure because they could be required for suppressive activity and/or limit Treg function. We evaluated the role of lymphocyte activation gene 3 (LAG3; CD223) on Tregs by generating mice in which LAG3 is absent on the cell surface of Tregs in a murine model of type 1 diabetes...
March 31, 2017: Science Immunology
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