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https://www.readbyqxmd.com/read/28446615/proliferation-of-pd-1-cd8-t-cells-in-peripheral-blood-after-pd-1-targeted-therapy-in-lung-cancer-patients
#1
Alice O Kamphorst, Rathi N Pillai, Shu Yang, Tahseen H Nasti, Rama S Akondy, Andreas Wieland, Gabriel L Sica, Ke Yu, Lydia Koenig, Nikita T Patel, Madhusmita Behera, Hong Wu, Megan McCausland, Zhengjia Chen, Chao Zhang, Fadlo R Khuri, Taofeek K Owonikoko, Rafi Ahmed, Suresh S Ramalingam
Exhausted T cells in chronic infections and cancer have sustained expression of the inhibitory receptor programmed cell death 1 (PD-1). Therapies that block the PD-1 pathway have shown promising clinical results in a significant number of advanced-stage cancer patients. Nonetheless, a better understanding of the immunological responses induced by PD-1 blockade in cancer patients is lacking. Identification of predictive biomarkers is a priority in the field, but whether peripheral blood analysis can provide biomarkers to monitor or predict patients' responses to treatment remains to be resolved...
April 26, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28444847/complement-dependence-of-murine-costimulatory-blockade-resistant-cellular-cardiac-allograft-rejection
#2
Nicholas Chun, Robert L Fairchild, Yansui Li, Jinhua Liu, Ming Zhang, William M Baldwin, Peter S Heeger
Building upon studies showing that ischemia/reperfusion-(IR)-injury is complement-dependent, we tested links among complement activation, transplant associated ischemia-reperfusion injury, and murine cardiac allograft rejection. We transplanted BALB/c hearts subjected to 8h cold ischemic storage (CIS) into CTLA4Ig-treated WT or c3(-/-) B6 recipients. Whereas allografts subjected to 8h CIS rejected in WT recipients with a median survival time (MST) of 37d, identically treated hearts survived >60d in c3(-/-) mice (p<0...
April 26, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28444111/pattern-recognition-receptors-immune-targets-to-enhance-cancer-immunotherapy
#3
T Shekarian, S Valsesia-Wittmann, J Brody, M C Michallet, S Depil, C Caux, A Marabelle
Durable tumor responses and significant levels of disease control rates have been described in more than 20 advanced/metastatic cancer types with B7-family immune checkpoint-targeted anti-CTLA-4, anti-PD-1, and anti-PD-L1 monoclonal antibodies. These results and the recent approvals of ipilimumab, pembrolizumab, nivolumab and atezolizumab are currently revolutionizing the way we envision the future of cancer care. However these clinical benefits are not observed in all cancer types and in every patient. Therefore, our clinical challenge is to identify therapeutic strategies which could overcome the primary and secondary resistances to these novel cancer immunotherapies...
April 21, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28439267/pulmonary-delivery-of-virosome-bound-antigen-enhances-antigen-specific-cd4-t-cell-proliferation-compared-to-liposome-bound-or-soluble-antigen
#4
Rebecca A M Blom, Mario Amacker, R Maarten van Dijk, Christian Moser, Philip A Stumbles, Fabian Blank, Christophe von Garnier
Pulmonary administration of biomimetic nanoparticles loaded with antigen may represent an effective strategy to directly modulate adaptive immune responses in the respiratory tract. Depending on the design, virosomes may not only serve as biomimetic antigen carriers but are also endowed with intrinsic immune-stimulatory properties. We designed fluorescently labeled influenza-derived virosomes and liposome controls coupled to the model antigen ovalbumin to investigate uptake, phenotype changes, and antigen processing by antigen-presenting cells exposed to such particles in different respiratory tract compartments...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28436935/tnf-superfamily-receptor-ox40-triggers-invariant-nkt-cell-pyroptosis-and-liver-injury
#5
Peixiang Lan, Yihui Fan, Yue Zhao, Xiaohua Lou, Howard P Monsour, Xiaolong Zhang, Yongwon Choi, Yaling Dou, Naoto Ishii, Rafik M Ghobrial, Xiang Xiao, Xian Chang Li
Tissue-resident immune cells play a key role in local and systemic immune responses. The liver, in particular, hosts a large number of invariant natural killer T (iNKT) cells, which are involved in diverse immune responses. However, the mechanisms that regulate survival and homeostasis of liver iNKT cells are poorly defined. Here we have found that liver iNKT cells constitutively express the costimulatory TNF superfamily receptor OX40 and that OX40 stimulation results in massive pyroptotic death of iNKT cells, characterized by the release of potent proinflammatory cytokines that induce liver injury...
April 24, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28427861/divergent-function-of-programmed-death-ligand-1-in-donor-tissue-versus-recipient-immune-system-in-a-murine-model-of-bronchiolitis-obliterans
#6
Katharina Schütte-Nütgen, Olaf Boenisch, Hakima Harrach, Alicia Casey, Indira Guleria, Nader Najafian, Mohamed H Sayegh, Craig J Gerard, Meera Subramaniam
Costimulatory molecules, such as the programmed death ligand (PD-L1), might exert differential effects on T-cell function, depending on the clinical setting and/or immunological environment. Given the impact of T cells on bronchiolitis obliterans (BO) in lung transplantation, we used an established tracheal transplant model inducing BO-like lesions to investigate the impact of PD-L1 on alloimmune responses and histopathological outcome in BO. In contrast to other transplant models in which PD-L1 generally shows protective functions, we demonstrated that PD-L1 has divergent effects depending on its location in donor versus recipient tissue...
April 17, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28421466/parathyroid-diseases-and-t-cells
#7
REVIEW
M Neale Weitzmann, Roberto Pacifici
PURPOSE OF REVIEW: This review summarizes studies into the permissive role of T cells in the bone catabolic effects of hyperparathyroidism and parathyroid hormone (PTH). RECENT FINDINGS: Work in animals combined with recent translational studies in humans now highlight the potent amplificatory action of T cells on PTH-induced bone resorption. Mechanistic animal studies reveal a complex pathway by which PTH exploits natural self-renewal functions of CD4(+) T cells, to drive TNFα production that promotes formation of IL-17A secreting Th17 T cells...
April 18, 2017: Current Osteoporosis Reports
https://www.readbyqxmd.com/read/28418904/a-consensus-hemagglutinin-based-vaccine-delivered-by-an-attenuated-salmonella-mutant-protects-chickens-against-heterologous-h7n1-influenza-virus
#8
Kim Je Hyoung, Irshad Ahmed Hajam, John Hwa Lee
H7N3 and H7N7 are highly pathogenic avian influenza (HPAI) viruses and have posed a great threat not only for the poultry industry but for the human health as well. H7N9, a low pathogenic avian influenza (LPAI) virus, is also highly pathogenic to humans, and there is a great concern that these H7 subtypes would acquire the ability to spread efficiently between humans, thereby becoming a pandemic threat. A vaccine candidate covering all the three subtypes must, therefore, be an integral part of any pandemic preparedness plan...
March 18, 2017: Oncotarget
https://www.readbyqxmd.com/read/28415767/unique-properties-of-thymic-antigen-presenting-cells-promote-epigenetic-imprinting-of-alloantigen-specific-regulatory-t-cells
#9
Garima Garg, Eirini Nikolouli, Matthias Hardtke-Wolenski, Aras Toker, Naganari Ohkura, Michael Beckstette, Takahisa Miyao, Robert Geffers, Stefan Floess, Norbert Gerdes, Esther Lutgens, Anke Osterloh, Shohei Hori, Shimon Sakaguchi, Elmar Jaeckel, Jochen Huehn
Regulatory T cells (Tregs) are potential immunotherapeutic candidates to induce transplantation tolerance. However, stability of Tregs still remains contentious and may potentially restrict their clinical use. Recent work suggested that epigenetic imprinting of Foxp3 and other Treg-specific signature genes is crucial for stabilization of immunosuppressive properties of Foxp3+ Tregs, and that these events are initiated already during early stages of thymic Treg development. However, the mechanisms governing this process remain largely unknown...
March 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28415754/gene-modified-nk-92mi-cells-expressing-a-chimeric-cd16-bb-%C3%AE-or-cd64-bb-%C3%AE-receptor-exhibit-enhanced-cancer-killing-ability-in-combination-with-therapeutic-antibody
#10
Ying Chen, Fengtao You, Licui Jiang, Jialu Li, Xuejun Zhu, Yangyi Bao, Xiang Sun, Xiaowen Tang, Huimin Meng, Gangli An, Bozhen Zhang, Lin Yang
Natural killer (NK) cells play a pivotal role in monoclonal antibody-mediated immunotherapy through the antibody-dependent cell-mediated cytotoxicity (ADCC) mechanism. NK-92MI is an interleukin-2 (IL-2)-independent cell line, which was derived from NK-92 cells with superior cytotoxicity toward a wide range of tumor cells in vitro and in vivo. Nonetheless, the Fc-receptor (CD16) that usually mediates ADCC is absent in NK-92 and NK-92MI cells. To apply NK-92MI cell-based immunotherapy to cancer treatment, we designed and generated two chimeric receptors in NK-92MI cells that can bind the Fc portion of human immunoglobulins...
March 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28408783/prokaryotic-expression-of-the-extracellular-domain-of-porcine-programmed-death-1-pd-1-and-its-ligand-pd-l1-and-identification-of-the-binding-with-peripheral-blood-mononuclear-cells-in-vitro
#11
Yan-Ping Zhu, Feng Yue, Yong He, Peng Li, Yuan Yang, Yu-Ting Han, Yan-Fang Zhang, Guo-Peng Sun, Dong-Guang Guo, Mei Yin, Xuan-Nian Wang
Programmed cell death protein 1 (PD-1), a costimulatory molecule of the CD28 family, has 2 ligands, PD-L1 and PD-L2. Our previous studies showed that the expression of PD-1 and PD-L1 is up-regulated during viral infection in pigs. Extensive studies have shown that blockade of the PD-1/PD-L1 pathways by anti-PD-L1 antibody or soluble PD-1 restores exhausted T-cells in humans and mice. In the present study the extracellular domains of PD-1 and PD-L1 were used to evaluate the binding of PD-1 and PD-L1 with peripheral blood mononuclear cells (PBMCs)...
April 2017: Canadian Journal of Veterinary Research, Revue Canadienne de Recherche Vétérinaire
https://www.readbyqxmd.com/read/28405609/preconditioned-mesenchymal-stem-cells-treat-myasthenia-gravis-in-a-humanized-preclinical-model
#12
Muriel Sudres, Marie Maurer, Marieke Robinet, Jacky Bismuth, Frédérique Truffault, Diane Girard, Nadine Dragin, Mohamed Attia, Elie Fadel, Nicola Santelmo, Camille Sicsic, Talma Brenner, Sonia Berrih-Aknin
Myasthenia gravis (MG) with anti-acetylcholine receptor (AChR) Abs is an autoimmune disease characterized by severe defects in immune regulation and thymic inflammation. Because mesenchymal stem cells (MSCs) display immunomodulatory features, we investigated whether and how in vitro-preconditioned human MSCs (cMSCs) could treat MG disease. We developed a new humanized preclinical model by subcutaneously grafting thymic MG fragments into immunodeficient NSG mice (NSG-MG model). Ninety percent of the animals displayed human anti-AChR Abs in the serum, and 50% of the animals displayed MG-like symptoms that correlated with the loss of AChR at the muscle endplates...
April 6, 2017: JCI Insight
https://www.readbyqxmd.com/read/28404894/induction-and-characterization-of-anti-tumor-endothelium-immunity-elicited-by-vallovax-therapeutic-cancer-vaccine
#13
Samuel C Wagner, Thomas E Ichim, Vladimir Bogin, Wei-Ping Min, Francisco Silva, Amit N Patel, Santosh Kesari
ValloVax is a placental endothelium derived vaccine which induces tissue-nonspecific antitumor immunity by blocking tumor angiogesis. To elucidate mechanisms of action, we showed that production of ValloVax, which involves treating placental endothelial cells with IFN-gamma, results in upregulation of HLA and costimulatory molecules. It was shown that in mixed lymphocyte reaction, ValloVax induces Type I cytokines and allo-proliferative responses. Plasma from ValloVax immunized mice was capable of killing in vitro tumor-like endothelium but not control endothelium...
February 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/28397730/programmed-cell-death-1-programmed-death-ligand-1-pathway-a-new-target-for-sepsis
#14
REVIEW
Qiang Liu, Chun-Sheng Li
OBJECTIVE: Sepsis remains a leading cause of death in many Intensive Care Units worldwide. Immunosuppression has been a primary focus of sepsis research as a key pathophysiological mechanism. Given the important role of the negative costimulatory molecules programmed cell death-1 (PD-1) and programmed death-ligand 1 (PD-L1) in the occurrence of immunosuppression during sepsis, we reviewed literatures related to the PD-1/PD-L1 pathway to examine its potential as a new target for sepsis treatment...
April 20, 2017: Chinese Medical Journal
https://www.readbyqxmd.com/read/28396662/the-role-of-dendritic-cell-maturation-in-the-induction-of-insulin-dependent-diabetes-mellitus
#15
REVIEW
Jacques C Mbongue, Hector A Nieves, Timothy W Torrez, William H R Langridge
Dendritic cells (DCs) are the dominant class of antigen-presenting cells in humans and are largely responsible for the initiation and guidance of innate and adaptive immune responses involved in maintenance of immunological homeostasis. Immature dendritic cells (iDCs) phagocytize pathogens and toxic proteins and in endosomal vesicles degrade them into small fragments for presentation on major histocompatibility complex (MHC) II receptor molecules to naïve cognate T cells (Th0). In addition to their role in stimulation of immunity, DCs are involved in the induction and maintenance of immune tolerance toward self-antigens...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28395442/-pd-1-pd-l1-expression-and-its-implications-in-patients-with-chronic-lymphocytic-leukemia
#16
J H Li, N N Pang, Z H Zhang, R Zhang, G Chen, J H Qu
Objective: To observe the expression levels of PD-1/PD-L1 costimulatory molecules and explore the clinical significance in patients with chronic lymphocytic leukemia (CLL) . Methods: The expression of PD-1/PD-L1 in peripheral blood CD8(+) T cells, CD4(+)T cells, CD19(+)B, and dendrites cells (DC) was detected by flow cytometry in 57 CLL patients and 20 healthy controls. The correlations of PD-1/PD-L1 expression with disease stage, CD38 expression, ZAP-70 expression, chromosome karyotype abnormality and β(2)-MG expression were analyzed...
March 14, 2017: Zhonghua Xue Ye Xue za Zhi, Zhonghua Xueyexue Zazhi
https://www.readbyqxmd.com/read/28392507/gene-and-protein-expression-of-a-soluble-form-of-ctla-4-in-a-healthy-dog
#17
Michihito Tagawa, Yuhei Yamamoto, Genya Shimbo, Aiko Iguchi, Xuenan Xuan, Mizuki Tomihari, Kazuro Miyahara
Cytotoxic T lymphocyte associated gene-4 (CTLA-4) is a costimulatory molecule, expressed on the surface of activated T cells that negatively regulates T cell activation. In humans, alternative splicing of the CTLA-4 gene generates two major isoforms of mRNA, and a soluble form of CTLA-4 (sCTLA-4) was detected in normal human serum. We describe alternatively spliced mRNA expressed in peripheral blood mononuclear cells obtained from a healthy dog lacking the transmembrane domain coded by exon 3 of the CTLA-4 gene...
April 7, 2017: Journal of Veterinary Medical Science
https://www.readbyqxmd.com/read/28383653/immune-modulatory-micrornas-involved-in-tumor-attack-and-tumor-immune-escape
#18
Stefan B Eichmüller, Wolfram Osen, Ofer Mandelboim, Barbara Seliger
Current therapies against cancer utilize the patient's immune system for tumor eradication. However, tumor cells can evade immune surveillance of CD8+ T and/or natural killer (NK) cells by various strategies. These include the aberrant expression of human leukocyte antigen (HLA) class I antigens, co-inhibitory or costimulatory molecules, and components of the interferon (IFN) signal transduction pathway. In addition, alterations of the tumor microenvironment could interfere with efficient antitumor immune responses by downregulating or inhibiting the frequency and/or functional activity of immune effector cells and professional antigen-presenting cells...
April 5, 2017: Journal of the National Cancer Institute
https://www.readbyqxmd.com/read/28378805/neonatal-mice-possess-two-phenotypically-and-functionally-distinct-lung-migratory-cd103-dendritic-cell-populations-following-respiratory-infection
#19
T J Ruckwardt, K M Morabito, E Bar-Haim, D Nair, B S Graham
The CD103(+) subset of lung-migratory dendritic cells (DCs) plays an important role in the generation of CD8(+) T cell responses following respiratory infection. Here, we demonstrate that the dependence on CD103(+) DCs for stimulation of RSV-specific T cells is both epitope and age-dependent. CD103(+) DCs in neonatal mice develop two phenotypically and functionally distinct populations following respiratory infection. Neonatal CD103(+) DCs expressing low levels of CD103 (CD103lo DCs) and other lineage and maturation markers including costimulatory molecules are phenotypically immature and functionally limited...
April 5, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/28369782/immune-checkpoint-proteins-exploring-their-therapeutic-potential-to-regulate-atherosclerosis
#20
REVIEW
A C Foks, J Kuiper
The immune system provides a large diversity of immune checkpoint proteins, which involve both costimulatory and inhibitory proteins. Costimulatory proteins can promote cell survival, cell cycle progression and differentiation to effector and memory cells, whereas inhibitory proteins terminate these processes to halt ongoing inflammation. Immune checkpoint proteins play a pivotal role in atherosclerosis by regulating the activation and proliferation of various immune and non-immune cells, such as T cells, macrophages and platelets...
March 30, 2017: British Journal of Pharmacology
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