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https://www.readbyqxmd.com/read/29150240/dichotomous-expression-of-tnf-superfamily-ligands-on-antigen-presenting-cells-controls-post-priming-anti-viral-cd4-t-cell-immunity
#1
Yu-Han Chang, Kuan Chung Wang, Kuan-Lun Chu, Derek L Clouthier, Anh T Tran, Miguel S Torres Perez, Angela C Zhou, Ali A Abdul-Sater, Tania H Watts
T cell antigen-presenting cell (APC) interactions early during chronic viral infection are crucial for determining viral set point and disease outcome, but how and when different APC subtypes contribute to these outcomes is unclear. The TNF receptor superfamily (TNFRSF) member GITR is important for CD4(+) T cell accumulation and control of chronic lymphocytic choriomeningitis virus (LCMV). We found that type I interferon (IFN-I) induced TNFSF ligands GITRL, 4-1BBL, OX40L, and CD70 predominantly on monocyte-derived APCs and CD80 and CD86 predominantly on classical dendritic cells (cDCs)...
November 13, 2017: Immunity
https://www.readbyqxmd.com/read/29141863/eight-color-multiplex-immunohistochemistry-for-simultaneous-detection-of-multiple-immune-checkpoint-molecules-within-the-tumor-microenvironment
#2
Mark A J Gorris, Altuna Halilovic, Katrin Rabold, Anne van Duffelen, Iresha N Wickramasinghe, Dagmar Verweij, Inge M N Wortel, Johannes C Textor, I Jolanda M de Vries, Carl G Figdor
Therapies targeting immune checkpoint molecules CTLA-4 and PD-1/PD-L1 have advanced the field of cancer immunotherapy. New mAbs targeting different immune checkpoint molecules, such as TIM3, CD27, and OX40, are being developed and tested in clinical trials. To make educated decisions and design new combination treatment strategies, it is vital to learn more about coexpression of both inhibitory and stimulatory immune checkpoints on individual cells within the tumor microenvironment. Recent advances in multiple immunolabeling and multispectral imaging have enabled simultaneous analysis of more than three markers within a single formalin-fixed paraffin-embedded tissue section, with accurate cell discrimination and spatial information...
November 15, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29141217/th1-like-plasmodium-specific-memory-cd4-t-cells-support-humoral-immunity
#3
Ryan A Zander, Rahul Vijay, Angela D Pack, Jenna J Guthmiller, Amy C Graham, Scott E Lindner, Ashley M Vaughan, Stefan H I Kappe, Noah S Butler
Effector T cells exhibiting features of either T helper 1 (Th1) or T follicular helper (Tfh) populations are essential to control experimental Plasmodium infection and are believed to be critical for resistance to clinical malaria. To determine whether Plasmodium-specific Th1- and Tfh-like effector cells generate memory populations that contribute to protection, we developed transgenic parasites that enable high-resolution study of anti-malarial memory CD4 T cells in experimental models. We found that populations of both Th1- and Tfh-like Plasmodium-specific memory CD4 T cells persist...
November 14, 2017: Cell Reports
https://www.readbyqxmd.com/read/29118006/the-immunobiology-of-cd27-and-ox40-and-their-potential-as-targets-for-cancer-immunotherapy
#4
Sarah L Buchan, Anne Rogel, Aymen Al-Shamkhani
In recent years monoclonal antibodies (mAbs) able to reinvigorate anti-tumor T cell immunity have heralded a paradigm shift in cancer treatment. The most high profile of these mAbs block the inhibitory checkpoint receptors PD-1 and CTLA-4 and have improved life expectancy for patients across a range of tumor types. However, it is becoming increasingly clear that failure of some patients to respond to checkpoint inhibition is due to inadequate T-cell priming. For full T-cell activation two signals must be received and ligands providing the second of these signals, termed costimulation, are often lacking in tumors...
November 8, 2017: Blood
https://www.readbyqxmd.com/read/29100993/hepatitis-c-virus-induced-natural-killer-cell-proliferation-involves-monocyte-derived-cells-and-the-ox40-ox40l-axis
#5
Julia Pollmann, Jana-Julia Götz, Daniel Rupp, Otto Strauss, Markus Granzin, Oliver Grünvogel, Pascal Mutz, Catharina Kramer, Felix Lasitschka, Volker Lohmann, Niklas K Björkström, Robert Thimme, Ralf Bartenschlager, Adelheid Cerwenka
BACKGROUND AND AIMS: Natural killer (NK) cells are found at increased frequencies in hepatitis C virus (HCV)-infected patients. NK cell activation was shown to correlate with HCV clearance and to predict favourable treatment response. The aim of our study was to dissect mechanisms leading to NK cell activation and proliferation in response to HCV. METHODS: NK cell phenotype, proliferation, and function were assessed after six-day co-culture of human peripheral blood mononuclear cells (PBMCs) with HCV-replicon containing Huh6 hepatoblastoma cells or HCV-infected Huh7...
October 31, 2017: Journal of Hepatology
https://www.readbyqxmd.com/read/29092058/synergy-of-vaccination-and-agonist-ox40-treatment-toward-a-mechanism-driven-combination-of-glioma-immunotherapy
#6
Katrin Deumelandt, Michael Platten, Katharina Ochs
No abstract text is available yet for this article.
October 28, 2017: Neuro-oncology
https://www.readbyqxmd.com/read/29065175/comparative-analysis-of-activation-induced-marker-aim-assays-for-sensitive-identification-of-antigen-specific-cd4-t-cells
#7
COMPARATIVE STUDY
Samantha Reiss, Amy E Baxter, Kimberly M Cirelli, Jennifer M Dan, Antigoni Morou, Audrey Daigneault, Nathalie Brassard, Guido Silvestri, Jean-Pierre Routy, Colin Havenar-Daughton, Shane Crotty, Daniel E Kaufmann
The identification and study of antigen-specific CD4 T cells, both in peripheral blood and in tissues, is key for a broad range of immunological research, including vaccine responses and infectious diseases. Detection of these cells is hampered by both their rarity and their heterogeneity, in particular with regards to cytokine secretion profiles. These factors prevent the identification of the total pool of antigen-specific CD4 T cells by classical methods. We have developed assays for the highly sensitive detection of such cells by measuring the upregulation of surface activation induced markers (AIM)...
2017: PloS One
https://www.readbyqxmd.com/read/29052782/clinical-and-immunologic-evaluation-of-three-metastatic-melanoma-patients-treated-with-autologous-melanoma-reactive-tcr-transduced-t-cells
#8
Tamson Moore, Courtney Regan Wagner, Gina M Scurti, Kelli A Hutchens, Constantine Godellas, Ann Lau Clark, Elizabeth Motunrayo Kolawole, Lance M Hellman, Nishant K Singh, Fernando A Huyke, Siao-Yi Wang, Kelly M Calabrese, Heather D Embree, Rimas Orentas, Keisuke Shirai, Emilia Dellacecca, Elizabeth Garrett-Mayer, Mingli Li, Jonathan M Eby, Patrick J Stiff, Brian D Evavold, Brian M Baker, I Caroline Le Poole, Boro Dropulic, Joseph I Clark, Michael I Nishimura
Malignant melanoma incidence has been increasing for over 30 years, and despite promising new therapies, metastatic disease remains difficult to treat. We describe preliminary results from a Phase I clinical trial (NCT01586403) of adoptive cell therapy in which three patients received autologous CD4(+) and CD8(+) T cells transduced with a lentivirus carrying a tyrosinase-specific TCR and a marker protein, truncated CD34 (CD34t). This unusual MHC Class I-restricted TCR produces functional responses in both CD4(+) and CD8(+) T cells...
October 20, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/29045495/correction-pd-1-blockade-and-ox40-triggering-synergistically-protects-against-tumor-growth-in-a-murine-model-of-ovarian-cancer
#9
Zhiqiang Guo, Xin Wang, Dali Cheng, Zhijun Xia, Meng Luan, Shulan Zhang
[This corrects the article DOI: 10.1371/journal.pone.0089350.].
2017: PloS One
https://www.readbyqxmd.com/read/29038249/anti-pd-1-antibody-treatment-promotes-clearance-of-persistent-cryptococcal-lung-infection-in-mice
#10
Jonathan A Roussey, Steven P Viglianti, Seagal Teitz-Tennenbaum, Michal A Olszewski, John J Osterholzer
Activation of immunomodulatory pathways in response to invasive fungi can impair clearance and promote persistent infections. The programmed cell death protein-1 (PD-1) signaling pathway inhibits immune effector responses against tumors, and immune checkpoint inhibitors that block this pathway are being increasingly used as cancer therapy. The objective of this study was to investigate whether this pathway contributes to persistent fungal infection and to determine whether anti-PD-1 Ab treatment improves fungal clearance...
November 15, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29030331/on-ox40-and-pd-1-combination-why-should-ox40-be-first-in-sequence
#11
Mario P Colombo
The larger fraction of patients treated with immune checkpoint inhibitors remain nonresponding eventually. Combination of checkpoint inhibitor and costimulatory antibodies is thought additive, but for such effect, they may require to be given in the right sequence. Clin Cancer Res; 23(20); 5999-6001. ©2017 AACRSee related article by Messenheimer et al., p. 6165.
October 15, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29028770/expression-and-clinical-correlations-of-co-stimulatory-molecules-on-peripheral-t-lymphocyte-subsets-of-early-stage-severe-sepsis-a-prospective-observational-study
#12
Yi Lu, Le An, Qiang Liu, Chunsheng Li
OBJECTIVE: To investigate the expression and clinical correlations of co-stimulatory molecules on peripheral T cell subsets of severe sepsis (SS) patients. METHODS: Blood samples of patients with community-acquired pneumonia associated SS and healthy controls (HCs) were analyzed. SS patients were followed up for 28 days. Co-stimulatory molecules expression on T cell subsets was determined by flow cytometry analysis. The clinical correlations of these parameters were examined...
October 12, 2017: Shock
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
#13
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/28929455/role-of-mast-cells-in-regulation-of-t-cell-responses-in-experimental-and-clinical-settings
#14
REVIEW
Daniel Elieh Ali Komi, Korneel Grauwet
Mast cells secrete a wide spectrum of stored or newly synthesized pro-inflammatory, anti-inflammatory, and/or immunosuppressive mediators and express several costimulatory and inhibitory surface molecules. Mast cells finely tune activities of T cells, B cells, and regulatory cells and effectively contribute to the development of different T cell-associated responses by influencing their recruitment, activation, proliferation, and differentiation. The interaction between mast cells and T cells, with regard to cellular functionality and immune responses, can be assessed in both activating and inhibitory regulations...
September 19, 2017: Clinical Reviews in Allergy & Immunology
https://www.readbyqxmd.com/read/28927419/tumor-necrosis-factor-superfamily-ligand-mrna-expression-profiles-differ-between-humans-and-mice-during-homeostasis-and-between-various-murine-kidney-injuries
#15
Satish Kumar Devarapu, Julia Felicitas Grill, Junhui Xie, Marc Weidenbusch, Mohsen Honarpisheh, Volker Vielhauer, Hans-Joachim Anders, Shrikant R Mulay
BACKGROUND: Several tumour necrosis factor (TNF) based therapeutics have already been approved for human use and several others are emerging. Therefore, we determined the mRNA expression levels of the TNF superfamily ligands (TNFSF) - e.g. TNF-α, lymphotoxin (LT)-α, LT-β, Fas-L (CD95-L), TNF-related apoptosis-inducing ligand (TRAIL), TNF-related weak inducer of apoptosis (TWEAK), 4-1BBL, OX40-L (CD252) and amyloid precursor protein (APP) in healthy human and mouse solid organs. METHODS: We used quantitative real time-PCR to analyse mRNA expression levels of TNFSF ligands...
September 19, 2017: Journal of Biomedical Science
https://www.readbyqxmd.com/read/28921877/analysis-of-infantile-fibrosarcoma-reveals-extensive-t-cell-responses-within-tumors-implications-for-immunotherapy
#16
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/28915720/pseudoprogression-in-microsatellite-instability-high-colorectal-cancer-during-treatment-with-combination-t-cell-mediated-immunotherapy-a-case-report-and-literature-review
#17
Young Kwang Chae, Si Wang, Halla Nimeiri, Aparna Kalyan, Francis J Giles
Evading tumor-mediated immunosuppression through antibodies to immune checkpoints has shown clinical benefit in patients with select solid tumors. There is a heterogeneity of responses in patients receiving immunotherapy, including pseudoprogression in which the tumor burden increases initially before decreasing to reach disease control. The characteristics and basis of pseudoprogression, however, remains poorly understood. We hereby report a case of microsatellite instability (MSI)-high metastatic colorectal cancer treated with combination of OX40 agonist and programmed death ligand-1 (PD-L1) antagonist that demonstrated pseudoprogression reaching 163% increase from baseline tumor burden...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28905118/administration-of-low-dose-combination-anti-ctla4-anti-cd137-and-anti-ox40-into-murine-tumor-or-proximal-to-the-tumor-draining-lymph-node-induces-systemic-tumor-regression
#18
Jonathan P O Hebb, Adriane R Mosley, Felipe Vences-Catalán, Narendiran Rajasekaran, Anna Rosén, Peter Ellmark, Dean W Felsher
The delivery of immunomodulators directly into the tumor potentially harnesses the existing antigen, tumor-specific infiltrating lymphocytes, and antigen presenting cells. This can confer specificity and generate a potent systemic anti-tumor immune response with lower doses and less toxicity compared to systemic administration, in effect an in situ vaccine. Here, we test this concept using the novel combination of immunomodulators anti-CTLA4, -CD137, and -OX40. The triple combination administered intratumorally at low doses to one tumor of a dual tumor mouse model had dramatic local and systemic anti-tumor efficacy in lymphoma (A20) and solid tumor (MC38) models, consistent with an abscopal effect...
September 13, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28892047/a-system-for-detecting-high-impact-low-frequency-mutations-in-primary-tumors-and-metastases
#19
M Anjanappa, Y Hao, E R Simpson, P Bhat-Nakshatri, J B Nelson, S A Tersey, R G Mirmira, A A Cohen-Gadol, M R Saadatzadeh, L Li, F Fang, K P Nephew, K D Miller, Y Liu, H Nakshatri
Tumor complexity and intratumor heterogeneity contribute to subclonal diversity. Despite advances in next-generation sequencing (NGS) and bioinformatics, detecting rare mutations in primary tumors and metastases contributing to subclonal diversity is a challenge for precision genomics. Here, in order to identify rare mutations, we adapted a recently described epithelial reprograming assay for short-term propagation of epithelial cells from primary and metastatic tumors. Using this approach, we expanded minor clones and obtained epithelial cell-specific DNA/RNA for quantitative NGS analysis...
September 11, 2017: Oncogene
https://www.readbyqxmd.com/read/28875845/new-trends-in-anti-cancer-therapy-combining-conventional-chemotherapeutics-with-novel-immunomodulators
#20
Amy L Wilson, Magdalena Plebanski, Andrew N Stephens
Cancer is one of the leading causes of death worldwide, and current research has focused on the discovery of novel approaches to effectively treat this disease. Recently, a considerable number of clinical trials have demonstrated the success of immunomodulatory therapies for the treatment of cancer. Monoclonal antibodies can target components of the immune system to either i) agonise co-stimulatory molecules, such as CD137, OX40 and CD40; or ii) inhibit immune checkpoints, such as cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), programmed cell death-1 (PD-1) and its corresponding ligand PD-L1...
August 29, 2017: Current Medicinal Chemistry
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