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T cell inhibitory pathway

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https://www.readbyqxmd.com/read/28454312/treatment-with-a-selenium-platinum-compound-induced-t-cell-acute-lymphoblastic-leukemia-lymphoma-cells-apoptosis-through-the-mitochondrial-signaling-pathway
#1
Feifei Wu, Wei Cao, Huaping Xu, Mingxia Zhu, Jing Wang, Xiaoyan Ke
T-cell acute lymphoblastic leukemia/lymphoma (T-ALL/LBL) is an aggressive hematological disorder that is sensitive to chemotherapy; however, it exhibits frequent relapse rates. Platinum-containing therapeutics are the first-line salvage regimens used in the treatment of relapsed or refractory T-ALL/LBL. The selenium-platinum compound EG-Se/Pt is obtained from the combination of selenium-containing molecules (EG-Se) with cisplatin (CDDP); however, its anticancer properties have been poorly investigated. In the present study, the Cell Counting Kit-8 assay was used to evaluate the inhibitory effect of treatment with EG-Se/Pt on cell viability...
March 2017: Oncology Letters
https://www.readbyqxmd.com/read/28454090/peroxiredoxin-6-overexpression-attenuates-lipopolysaccharide-induced-acute-kidney-injury
#2
Dong Hun Lee, Ju Ho Park, Sang Bae Han, Do Young Yoon, Yu Yeon Jung, Jin Tae Hong
Peroxiredoxin 6 (PRDX6) is a member of the PRDX family of antioxidant enzymes and correlated with inflammatory response. Therefore, we investigated the role of PRDX6 during lipopolysaccharide (LPS)-induced acute kidney injury. Both 3 months aged PRDX6-overexpressing transgenic mice (PRDX6 mice) and wild type (WT) mice had acute renal injury induced by intraperitoneal injection of LPS (10 mg/kg)., PRDX6 mice showed decreased mortality and renal injury following LPS challenge compared to WT mice. Furthermore, infiltration of macrophages, T-cells and neutrophils, and the number of apoptotic cells were more decreased by LPS treatment in PRDX6 mice than in WT mice...
April 10, 2017: Oncotarget
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
#3
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/28437437/use-of-short-interfering-rna-delivered-by-cationic-liposomes-to-enable-efficient-down-regulation-of-ptpn22-gene-in-human-t-lymphocytes
#4
Valentina Perri, Marsha Pellegrino, Francesca Ceccacci, Anita Scipioni, Stefania Petrini, Elena Gianchecchi, Anna Lo Russo, Serena De Santis, Giovanna Mancini, Alessandra Fierabracci
Type 1 diabetes and thyroid disease are T cell-dependent autoimmune endocrinopathies. The standard substitutive administration of the deficient hormones does not halt the autoimmune process; therefore, development of immunotherapies aiming to preserve the residual hormonal cells, is of crucial importance. PTPN22 C1858T mutation encoding for the R620W lymphoid tyrosine phosphatase variant, plays a potential pathophysiological role in autoimmunity. The PTPN22 encoded protein Lyp is a negative regulator of T cell antigen receptor signaling; R620W variant, leading to a gain of function with paradoxical reduced T cell activation, may represent a valid therapeutic target...
2017: PloS One
https://www.readbyqxmd.com/read/28429196/expression-of-programmed-cell-death-protein-1-by-tumor-infiltrating-lymphocytes-and-tumor-cells-is-associated-with-advanced-tumor-stage-in-patients-with-esophageal-adenocarcinoma
#5
Dagmar Kollmann, Desislava Ignatova, Julia Jedamzik, Yun-Tsan Chang, Gerd Jomrich, Matthias Paireder, Ivan Kristo, Dmitry Kazakov, Michal Michal, Antonio Cozzio, Wolfram Hoetzenecker, Tobias Schatton, Reza Asari, Matthias Preusser, Emmanuella Guenova, Sebastian F Schoppmann
BACKGROUND: Despite recent advances in the therapy for adenocarcinoma of the esophagogastric junction (AEG), overall prognosis remains poor. Programmed cell death protein 1 (PD1) is a co-inhibitory receptor primarily expressed by T-cells. Tumor cells can escape anticancer immune responses by triggering the PD1 pathway. Moreover, PD1 receptor engagement on cancer cells may trigger tumor-intrinsic growth signals. This study aimed to evaluate the potential clinical relevance of PD1 expression by tumor-infiltrating lymphocytes (TILs) and cancer cells in the AEG...
April 20, 2017: Annals of Surgical Oncology
https://www.readbyqxmd.com/read/28413317/korean-red-ginseng-improves-atopic-dermatitis-like-skin-lesions-by-suppressing-expression-of-proinflammatory-cytokines-and-chemokines-in%C3%A2-vivo-and-in%C3%A2-vitro
#6
Ji-Ye Kee, Yong-Deok Jeon, Dae-Seung Kim, Yo-Han Han, Jinbong Park, Dong-Hyun Youn, Su-Jin Kim, Kwang Seok Ahn, Jae-Young Um, Seung-Heon Hong
BACKGROUND: The prevalence of allergic inflammatory diseases such as atopic dermatitis (AD), asthma, and allergic rhinitis worldwide has increased and complete recovery is difficult. Korean Red Ginseng, which is the heat-processed root of Panax ginseng Meyer, is widely and frequently used as a traditional medicine in East Asia. In this study, we investigated whether Korean Red Ginseng water extract (RGE) regulates the expression of proinflammatory cytokines and chemokines via the mitogen-activated protein kinases (MAPKs)/nuclear factor kappa B (NF-κB) pathway in allergic inflammation...
April 2017: Journal of Ginseng Research
https://www.readbyqxmd.com/read/28408143/tetrandrine-potentiates-the-glucocorticoid-pharmacodynamics-via-inhibiting-p-glycoprotein-and-mitogen-activated-protein-kinase-in-mitogen-activated-human-peripheral-blood-mononuclear-cells
#7
Wencheng Xu, Kehan Meng, Yuanchao Tu, Sachiko Tanaka, Kenji Onda, Kentaro Sugiyama, Toshihiko Hirano, Haruki Yamada
Glucocorticoids play significant roles in treatments of inflammatory and autoimmune diseases. Some patients show a poor or absent response even to high doses of glucocorticoids. The purpose of this study was to explore whether tetrandrine combined with glucocorticoids could be a new treatment strategy to resolve glucocorticoids resistance. Information on glucocorticoids sensitivity was usually obtained through mitogen-activated human peripheral blood mononuclear cells in cell culture procedures. Thus, human peripheral blood mononuclear cells was chosen as a model to study the immunosuppressive effect of methylprednisolone combined with tetrandrine, including the possible action mechanisms...
April 10, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28405520/the-immune-molecular-landscape-of-the-b7-and-tnfr-immunoregulatory-ligand-receptor-families-in-head-and-neck-cancer-a-comprehensive-overview-and-the-immunotherapeutic-implications
#8
Yu-Pei Chen, Jian Zhang, Ya-Qin Wang, Na Liu, Qing-Mei He, Xiao-Jing Yang, Ying Sun, Jun Ma
The B7 family and tumor necrosis factor receptor (TNFR) superfamily play a vital role in the T-cell co-stimulatory and co-inhibitory pathways, regulating T-cell activation, tolerance, and exhaustion; therapeutic modulation of these pathways is translated into effective new cancer treatments. Better understanding of the immune molecular landscapes of the B7 and TNFR families would guide head and neck immuno-oncology clinical research. We performed comprehensive molecular profiling of 10 B7 and 6 TNFR family members in head and neck cancer...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28405506/oral-delivery-of-tumor-microparticle-vaccines-activates-nod2-signaling-pathway-in-ileac-epithelium-rendering-potent-antitumor-t-cell-immunity
#9
Wenqian Dong, Huafeng Zhang, Xiaonan Yin, Yuying Liu, Degao Chen, Xiaoyu Liang, Xun Jin, Jiadi Lv, Jingwei Ma, Ke Tang, Zhuowei Hu, Xiaofeng Qin, Bo Huang
Exploiting gut mucosal immunity to design new antitumor vaccination strategy remains unexplored. Tumor cell-derived microparticles (T-MP) are natural biomaterials that are capable of delivering tumor antigens and innate signals to dendritic cells (DC) for tumor-specific T cell immunity. Here, we show that T-MPs by oral vaccination route effectively access and activate mucosal epithelium, leading to subsequent antitumor T cell responses. Oral vaccination of T-MPs generated potent inhibitory effect against the growth of B16 melanoma and CT26 colon cancer in mice, which required both T cell and DC activation...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28401068/modulation-of-tim-3-expression-by-antigen-dependent-and-independent-factors-on-t-cells-from-patients-with-chronic-hepatitis-b-virus-infection
#10
Jie Dong, Xiao-Fei Yang, Lin-Xu Wang, Xin Wei, An-Hui Wang, Chun-Qiu Hao, Huan-Jun Shen, Chang-Xing Huang, Ye Zhang, Jian-Qi Lian
T-cell immunoglobulin domain and mucin domain-containing molecule-3 (Tim-3) was up-regulated on viral specific T cells and contributed to T cells exhaustion during chronic hepatitis B virus (HBV) infection. However, modulation of Tim-3 expression was still not fully elucidated. To evaluate the potential viral and inflammatory factors involved in the inductor of Tim-3 expression on T cells, 76 patients with chronic HBV infection (including 40 chronic hepatitis B [CHB] and 36 asymptomatic HBV carriers [AsC]) and 40 of normal controls (NCs) were enrolled in this study...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/28400597/indicators-of-responsiveness-to-immune-checkpoint-inhibitors
#11
Bradley D Shields, Fade Mahmoud, Erin M Taylor, Stephanie D Byrum, Deepanwita Sengupta, Brian Koss, Giulia Baldini, Seth Ransom, Kyle Cline, Samuel G Mackintosh, Ricky D Edmondson, Sara Shalin, Alan J Tackett
Modulation of the immune system can produce anti-tumor responses in various cancer types, including melanoma. Recently, immune checkpoint inhibitors (ICI), in single agent and combination regimens, have produced durable and long-lasting clinical responses in a subset of metastatic melanoma patients. These monoclonal antibodies, developed against CTLA-4 and PD-1, block immune-inhibitory receptors on activated T-cells, amplifying the immune response. However, even when using anti-CTLA-4 and anti-PD-1 in combination, approximately half of patients exhibit innate resistance and suffer from disease progression...
April 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28395975/increased-soluble-cd226-in-sera-of-patients-with-cutaneous-t-cell-lymphoma-mediating-cytotoxic-activity-against-tumor-cells-via-cd155
#12
Naomi Takahashi, Makoto Sugaya, Hiraku Suga, Tomonori Oka, Makiko Kawaguchi, Tomomitsu Miyagaki, Hideki Fujita, Takashi Inozume, Shinichi Sato
Immune checkpoint therapy, which targets regulatory pathways in T cells to enhance antitumor immune responses, has led to important clinical advances. CD155 is expressed in various types of cancer and this surface molecule on tumor cells functions either as a co-stimulatory molecule or a co-inhibitory molecule, depending on its receptor. CD226, a CD155 ligand, is mainly expressed on NK cells and CD8(+) T cells, playing important roles in NK cell-mediated cytotoxicity. In this study, we investigated expression and function of CD155 and CD226 in cutaneous T-cell lymphoma (CTCL)...
April 7, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/28389502/dc-subset-specific-induction-of-t-cell-responses-upon-antigen-uptake-via-fc%C3%AE-receptors-in-vivo
#13
Christian H K Lehmann, Anna Baranska, Gordon F Heidkamp, Lukas Heger, Kirsten Neubert, Jennifer J Lühr, Alana Hoffmann, Katharina C Reimer, Christin Brückner, Simone Beck, Michaela Seeling, Melissa Kießling, Didier Soulat, Anne B Krug, Jeffrey V Ravetch, Jeanette H W Leusen, Falk Nimmerjahn, Diana Dudziak
Dendritic cells (DCs) are efficient antigen-presenting cells equipped with various cell surface receptors for the direct or indirect recognition of pathogenic microorganisms. Interestingly, not much is known about the specific expression pattern and function of the individual activating and inhibitory Fcγ receptors (FcγRs) on splenic DC subsets in vivo and how they contribute to the initiation of T cell responses. By targeting antigens to select activating and the inhibitory FcγR in vivo, we show that antigen uptake under steady-state conditions results in a short-term expansion of antigen-specific T cells, whereas under inflammatory conditions especially, the activating FcγRIV is able to induce superior CD4(+) and CD8(+) T cell responses...
April 7, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28389151/a-bromopyrrole-containing-diterpene-alkaloid-from-the-okinawan-marine-sponge-agelas-nakamurai-activates-the-insulin-pathway-in-huh-7-human-hepatoma-cells-by-inhibiting-protein-tyrosine-phosphatase-1b
#14
Hiroyuki Yamazaki, Syu-Ichi Kanno, Delfly B Abdjul, Michio Namikoshi
Agelasine G (1), a known bromine-containing diterpene alkaloid, was isolated as a new type of protein tyrosine phosphatase (PTP) 1B inhibitor together with ageline B (2), an inactive debromo-derivative of 1, from the marine sponge Agelas nakamurai collected at Iriomote Island in Okinawa, Japan. Further biological evaluations revealed that compound 1 exhibited selective inhibitory activity against PTP1B over T-cell PTP and CD45 phosphatase. Compound 1 also enhanced the insulin-stimulated phosphorylation levels of Akt in Huh-7 cells more strongly than compound 2...
March 18, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28388539/preferential-accumulation-of-regulatory-t-cells-with-highly-immunosuppressive-characteristics-in-breast-tumor-microenvironment
#15
Azharuddin Sajid Syed Khaja, Salman M Toor, Haytham El Salhat, Issam Faour, Navid Ul Haq, Bassam R Ali, Eyad Elkord
Immunosuppressive cells such as regulatory T cells (Tregs) have an ambiguous role in breast cancer prognosis, with studies reporting both positive and negative correlations between Treg infiltration and prognosis. This discrepancy could be due to the different immunosuppressive molecules present in these cells. In the present study, we phenotypically characterize different Treg subsets infiltrating the tumor microenvironment (TME), compared to adjacent normal tissue and peripheral blood of primary breast cancer (PBC) patients...
March 25, 2017: Oncotarget
https://www.readbyqxmd.com/read/28383653/immune-modulatory-micrornas-involved-in-tumor-attack-and-tumor-immune-escape
#16
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/28376477/osteopontin-promotes-cell-migration-and-invasion-and-inhibits-apoptosis-and-autophagy-in-colorectal-cancer-by-activating-the-p38-mapk-signaling-pathway
#17
Ren-Hong Huang, Ying-Jun Quan, Jin-Hong Chen, Ting-Feng Wang, Ming Xu, Min Ye, Hao Yuan, Chong-Jie Zhang, Xiao-Jian Liu, Zhi-Jun Min
BACKGROUND: Osteopontin (OPN) is highly expressed in colorectal cancer (CRC) and is associated with disease progression in vivo. High levels of OPN have been demonstrated to predict low survival rates in CRC. Autophagy is a process of self-digestion, which is thought to play a significant role in carcinogenesis. However, the mechanisms of OPN's effects on CRC cell autophagy have not been elucidated. Therefore, we aimed to investigate possible mechanisms of OPN's effects on CRC autophagy...
April 3, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28373842/breast-cancer-stem-like-cells-are-inhibited-by-diosgenin-a-steroidal-saponin-by-the-attenuation-of-the-wnt-%C3%AE-catenin-signaling-via-the-wnt-antagonist-secreted-frizzled-related-protein-4
#18
G Bhuvanalakshmi, Basappa, Kanchugarakoppal S Rangappa, Arun Dharmarajan, Gautam Sethi, Alan P Kumar, Sudha Warrier
Background: Identification of breast cancer stem cells as the chemo-resistant and tumor-initiating population represents an important milestone in approaching anticancer therapies. Targeting this minor subpopulation of chemo- and radio-resistant stem-like cells, termed as the cancer stem cells (CSCs) and their eradication could significantly enhance clinical outcomes. Most of the presently administered chemotherapeutics target the tumor bulk but are ineffective against the CSCs. We report here that diosgenin (DG), a naturally occurring steroidal saponin, could effectively inhibit CSCs from three breast cancer cell lines, MCF7, T47D and MDA-MB-231, by inducing apoptosis and inhibiting the CSC associated phenotypes...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28361123/tocilizumab-anti-il-6r-suppressed-tnf%C3%AE-production-by-human-monocytes-in-an-in-vitro-model-of-anti-hla-antibody-induced-antibody-dependent-cellular-cytotoxicity
#19
Bong-Ha Shin, Shili Ge, James Mirocha, Stanley C Jordan, Mieko Toyoda
BACKGROUND: We previously demonstrated that natural killer (NK) cells activated via FcγRIIIa (CD16) interactions with anti-HLA antibodies binding to peripheral blood mononuclear cells (PBMCs) in the in vitro antibody-dependent cellular cytotoxicity (ADCC) assay produced IFNγ. Here we investigate if other CD16 bearing cells are responsive to alloantigen via alloantibody in the in vitro ADCC and if the ADCC-induced cytokine reactions and cytotoxicity can be modified by the anti-interleukin 6 receptor (IL-6R) monoclonal antibody, Tocilizumab (TCZ)...
March 2017: Transplantation Direct
https://www.readbyqxmd.com/read/28349925/paroxetine-alleviates-t-lymphocyte-activation-and-infiltration-to-joints-of-collagen-induced-arthritis
#20
Qingtong Wang, Longsheng Wang, Li Wu, Mei Zhang, Shanshan Hu, Rui Wang, Yongsheng Han, Yujing Wu, Lingling Zhang, Xinming Wang, Wuyi Sun, Wei Wei
T cell infiltration to synovial tissue is an early pathogenic mechanism of rheumatoid arthritis (RA). In the present work, we reveal that G protein coupled receptor kinase 2 (GRK2) is abundantly expressed in T cells of collagen-induced arthritis (CIA). A GRK2 inhibitor, paroxetine protects the joints from inflammation and destruction, primarily through inhibition of both CD4(+) helper T (Th) cell and CD8(+) cytotoxic T (Tc) cell migration to synovial tissue. Meanwhile, paroxetine restores the balance of Th/Tc, effector Th (Theff)/ naïve Th (Thnaive) and effector Tc (Tceff)/ naïve Tc (Tcnaive) to equilibrium by elevating the frequency of Thnaive, Tcnaive and regulatory Th cells; reducing the increased Theff, activated Th and Tceff, having a similar effect as methotrexate (MTX)...
March 28, 2017: Scientific Reports
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