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PD-1 T cell

Anisha Daxini, Keri Cronin, Antoine G Sreih
Recent experimental and genetic studies have implicated the role of programmed cell death protein 1 (PD-1), programmed cell death protein-ligand 1 (PDL-1), and cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) in the pathogenesis of medium and large vessel vasculitis. This study sought to evaluate the occurrence and nature of vasculitis associated with cancer treatment using immune checkpoint inhibition (anti-PD-1, anti-PDL-1, and anti-CTLA4). A systematic review of the medical literature was conducted by searching all available clinical data up to February 2018 in several databases and search engines including Cochrane Library, Embase, Google Scholar, Medline, Scopus, Web of Science, and Clinicaltrials...
June 19, 2018: Clinical Rheumatology
Robert D Leone, Im-Meng Sun, Min-Hee Oh, Im-Hong Sun, Jiayu Wen, Judson Englert, Jonathan D Powell
Adenosine signaling via the A2a receptor (A2aR) is emerging as an important checkpoint of immune responses. The presence of adenosine in the inflammatory milieu or generated by the CD39/CD73 axis on tissues or T regulatory cells serves to regulate immune responses. By nature of the specialized metabolism of cancer cells, adenosine levels are increased in the tumor microenvironment and contribute to tumor immune evasion. To this end, small molecule inhibitors of the A2aR are being pursued clinically to enhance immunotherapy...
June 19, 2018: Cancer Immunology, Immunotherapy: CII
Aijuan Yan, Yu Zhang, Jingya Lin, Lu Song, Xijin Wang, Zhenguo Liu
Background: Neuroinflammation plays an important role in the pathogenesis of Parkinson's disease (PD). Inflammatory cytokines in the peripheral immune system can induce neuroinflammation in central nervous system (CNS). Whether the peripheral immune system is involved in PD is unclear. The present study investigated the contribution of the peripheral immune system to the neuronal loss in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP) model of PD. Methods: MPTP was intraperitoneally injected into mice to generate a PD model...
2018: Frontiers in Aging Neuroscience
Chao-Qun Liu, Jing Xu, Zhong-Guo Zhou, Li-Lian Jin, Xing-Juan Yu, Gang Xiao, Jie Lin, Shi-Mei Zhuang, Yao-Jun Zhang, Limin Zheng
BACKGROUND: Recent clinical studies have suggested that programmed death ligand 1 (PD-L1) expression in a tumour could be a potential biomarker for PD-L1/PD-1 blockade therapies. METHODS: To better characterise PD-L1 expression in hepatocellular carcinoma (HCC), we analysed its expression patterns in 453 HCC patients by double staining for CD68 and PD-L1 using the Tyramide Signal Amplification Systems combined with immunohistochemistry. We also investigated its correlation with clinical features, prognosis and immune status...
June 20, 2018: British Journal of Cancer
Yuan Li, Yang Du, Ting Sun, Huadan Xue, Zhengyu Jin, Jie Tian
BACKGROUND: Blockade of PD-1 receptor may provide proof of concepts for the activity of an immune-modulation approach for the treatment of breast cancer (BC). Zoledronic acid (ZA) has been proven to inhibit angiogenesis, invasion, and adhesion of tumor cells. The aim of this study was to investigate the potential of monoclonal antibody against T cell checkpoint PD-1 in combination with chemotherapeutic drug ZA in BC mouse model. METHODS: The 4 T1-fLuc mouse BC model was used in this study...
June 19, 2018: BMC Cancer
Anthony P Y Liu, Pamela P W Lee, Janette S Y Kwok, Rock Y Y Leung, Alan K S Chiang, Shau-Yin Ha, Daniel K L Cheuk, Godfrey C F Chan
Relapsed/refractory NB carries a bleak outcome, warranting novel treatment options. HaploHSCT induces a graft-versus-NB effect via natural killer cell alloreactivity. Review of patients with relapsed/refractory NB who underwent haploHSCT with ex vivo T-cell depletion in our unit from 2013 through 2018. Ten patients were identified (male=5; median age at haploHSCT=6.45 y, range: 3.49-11.02 y). Indications were relapsed in 7 and refractoriness in 3; disease status at haploHSCT was CR in 2, PR in 6, and PD in 2...
June 19, 2018: Pediatric Transplantation
Rebecca J Boohaker, Vijaya Sambandam, Isaac Segura, James Miller, Mark Suto, Bo Xu
We report here the rational design and validation of a peptide inhibitor to the PD-1/PD-L1 interaction as an attempt to develop a viable alternative to current inhibitory antibodies. We demonstrated, by biolayer interferometry and in silico docking simulations, that a PD-L1 peptide mimetic (PL120131) can interfere with the PD-1/PD-L1 interaction by binding to PD-1. We show that PL120131 is capable of inhibiting PD-1 mediated apoptotic signaling pathway and rescuing Jurkat cells and primary lymphocytes from apoptosis...
June 16, 2018: Cancer Letters
Christoph Renner, Frank Stenner
Patients with classical Hodgkin lymphoma (cHL) have an impaired cellular immune response as indicated by an anergic reaction against standard recall antigens and a diminished rejection reaction of allogeneic skin transplant. This clinical observation can be linked to the histopathological feature of cHL since the typical pattern of a cHL manifestation is characterized by sparse large CD30+ tumor-infiltrating Hodgkin-Reed-Sternberg (HRS) cells that are surrounded by a dense inflammatory immune microenvironment with mixed cellularity...
2018: Frontiers in Oncology
Jun Deng, Chaofan Fan, Xin Gao, Qunxiong Zeng, Ruru Guo, Yunbo Wei, Zhian Chen, Yanan Chen, Dongcheng Gong, Jia Feng, Yan Xia, Shifei Xiang, Shushi Gong, Lin Yuan, Wei Shen, Wenyan Shen, Lin Lin, Ting Jiang, Dongyi He, Liangjing Lu, Xiaoxiang Chen, Di Yu
Follicular helper T (Tfh) cells are the specialized CD4+ T cell subset that supports B cells to produce high-affinity antibodies and generate humoral memory. Not only is the function of Tfh cells instrumental to mount protect antibodies but also to support autoantibody production and promote systemic inflammation in autoimmune diseases. However, it remains unclear how the activation of Tfh cells is driven in autoimmune diseases. Here, we report that in patients with rheumatoid arthritis (RA), excessive generation of CXCR5+ PD-1+ memory Tfh cells was observed and the frequency of memory Tfh cells correlated with disease activity score calculator for RA (DAS28)...
2018: Frontiers in Immunology
Stella Lukas Yani, Michael Keller, Franz Leonard Melzer, Birgit Weinberger, Luca Pangrazzi, Sieghart Sopper, Klemens Trieb, Monia Lobina, Valeria Orrù, Edoardo Fiorillo, Francesco Cucca, Beatrix Grubeck-Loebenstein
CD4+ regulatory T cells have been intensively studied during aging, but little is still known about age-related changes of other regulatory T cell subsets. It was, therefore, the goal of the present study to analyze CD8+ human leukocyte antigen-antigen D related (HLADR)+ T cells in old age, a cell population reported to have suppressive activity and to be connected to specific genetic variants. We demonstrate a strong increase in the number of CD8+ HLADR+ T cells with age in a cohort of female Sardinians as well as in elderly male and female persons from Austria...
2018: Frontiers in Immunology
Qing Zhang, Jiacheng Bi, Xiaodong Zheng, Yongyan Chen, Hua Wang, Wenyong Wu, Zhengguang Wang, Qiang Wu, Hui Peng, Haiming Wei, Rui Sun, Zhigang Tian
Checkpoint blockade enhances effector T cell function and has elicited long-term remission in a subset of patients with a broad spectrum of cancers. TIGIT is a checkpoint receptor thought to be involved in mediating T cell exhaustion in tumors; however, the relevance of TIGIT to the dysfunction of natural killer (NK) cells remains poorly understood. Here we found that TIGIT, but not the other checkpoint molecules CTLA-4 and PD-1, was associated with NK cell exhaustion in tumor-bearing mice and patients with colon cancer...
June 18, 2018: Nature Immunology
Evidio Domingo-Musibay, Paari Murugan, Alessio Giubellino, Sandeep Sharma, Daniel Steinberger, Jianling Yuan, Matthew A Hunt, Emil Lou, Jeffrey S Miller
BACKGROUND: Sebaceous carcinoma is an aggressive adnexal skin tumor with a predilection for the eyelids and sebaceous glands of the head and neck. CASE PRESENTATION: A 73 year-old man presented with confusion and was found to have widely disseminated sebaceous carcinoma with metastases to brain, lungs, liver, bowel, lymph nodes, and bone. Following initial treatment of the brain metastases with surgery he received post-operative radiosurgery. He then began systemic immunotherapy with pembrolizumab...
June 19, 2018: Journal for Immunotherapy of Cancer
Robert D Leone, Leisha A Emens
Immune checkpoint antagonists (CTLA-4 and PD-1/PD-L1) and CAR T-cell therapies generate unparalleled durable responses in several cancers and have firmly established immunotherapy as a new pillar of cancer therapy. To extend the impact of immunotherapy to more patients and a broader range of cancers, targeting additional mechanisms of tumor immune evasion will be critical. Adenosine signaling has emerged as a key metabolic pathway that regulates tumor immunity. Adenosine is an immunosuppressive metabolite produced at high levels within the tumor microenvironment...
June 18, 2018: Journal for Immunotherapy of Cancer
Tomohiro Okagawa, Satoru Konnai, Asami Nishimori, Naoya Maekawa, Shinya Goto, Ryoyo Ikebuchi, Junko Kohara, Yasuhiko Suzuki, Shinji Yamada, Yukinari Kato, Shiro Murata, Kazuhiko Ohashi
Bovine leukemia virus (BLV) is a retrovirus that infects B cells in cattle and causes bovine leukosis after a long latent period. Progressive exhaustion of T cell functions is considered to facilitate disease progression of BLV infection. Programmed death-1 (PD-1) and lymphocyte activation gene-3 (LAG-3) are immunoinhibitory receptors that contribute to T-cell exhaustion caused by BLV infection in cattle. However, it is unclear whether the cooperation of PD-1 and LAG-3 accelerates disease progression of BLV infection...
June 19, 2018: Veterinary Research
Ahmed A Mostafa, Daniel E Meyers, Chandini M Thirukkumaran, Peter J Liu, Kathy Gratton, Jason Spurrell, Qiao Shi, Satbir Thakur, Don G Morris
As the current efficacy of oncolytic viruses (OVs) as monotherapy is limited, exploration of OVs as part of a broader immunotherapeutic treatment strategy for cancer is necessary. Here, we investigated the ability for immune checkpoint blockade to enhance the efficacy of oncolytic reovirus (RV) for the treatment of breast cancer (BrCa). In vitro, oncolysis and cytokine production were assessed in human and murine BrCa cell lines following RV exposure. Furthermore, RV-induced upregulation of tumor cell PD-L1 was evaluated...
June 15, 2018: Cancers
Nicholas Meti, Khashayar Esfahani, Nathalie A Johnson
Hodgkin Lymphoma (HL) is a unique disease entity both in its pathology and the young patient population that it primarily affects. Although cure rates are high, survivorship can be linked with significant recent long-term morbidity associated with both chemotherapy and radiotherapy. The most significant advances have been with the use of the anti-CD30-drug conjugated antibody brentuximab vedotin (BV) and inhibitors of program death 1 (PD-1). HL is genetically wired to up-regulate program death ligand 1 (PD-L1) in >95% of cases, creating a state of so-called “T cell exhaustion”, which can be reversed with immune checkpoint-inhibitor blockade...
June 15, 2018: Cancers
Min Dai, Ingegerd Hellstrom, Yuen Y Yip, Hans Olov Sjögren, Karl Erik Hellstrom
While immunomodulatory monoclonal antibodies (mAbs) have therapeutic efficacy against many tumors, few patients are cured. Attempting to improve their therapeutic efficacy we have applied the TC1 mouse lung carcinoma model and injected established subcutaneous tumors intratumorally with 3 weekly doses of various combinations of mAbs. Combinations of mAbs to CTLA4/PD1/CD137 (the 3 mAb combination) and to CTLA4/PD1/CD137/CD19 (the 4 mAb combination) were most efficacious to induce complete regression of both the injected tumor and an untreated tumor in the same mouse...
June 15, 2018: Journal of Immunotherapy
Marie Bettonville, Stefania d'Aria, Kathleen Weatherly, Paolo E Porporato, Jinyu Zhang, Sabrina Bousbata, Pierre Sonveaux, Michel Y Braun
Energy metabolism is essential for T cell function. However, how persistent antigenic stimulation affects T cell metabolism is unknown. Here, we report that long-term in vivo antigenic exposure induced a specific deficit in numerous metabolic enzymes. Accordingly, T cells exhibited low basal glycolytic flux and limited respiratory capacity. Strikingly, blockade of inhibitory receptor PD-1 stimulated the production of IFNγ in chronic T cells, but failed to shift their metabolism towards aerobic glycolysis, as observed in effector T cells...
June 18, 2018: ELife
Melanie Sarah Prout, Ryan L Kyle, Franca Ronchese, Graham Le Gros
Although IL-4 is long associated with CD4 Th2 immune responses, its role in Th2 subset development in non-lymphoid tissues is less clear. We sought to better define IL-4's role in CD4 Th2 responses by using transgenic mice that express a dual IL-4 AmCyan/IL-13 DsRed (IL-4AC/IL-13DR) fluorescent reporter on an IL-4-sufficient or IL-4-deficient background. Using primary Th2 immune response models against house dust mite or Nippostrongylus brasiliensis ( Nb ) allergens, we examined the requirement for IL-4 by each of the defined Th2 subsets in the antigen draining lymph node, skin, and lung tissues...
2018: Frontiers in Immunology
Ellen J Beswick, Carl Grim, Abinav Singh, Jose E Aguirre, Marissa Tafoya, Suimin Qiu, Gerhard Rogler, Rohini McKee, Von Samedi, Thomas Y Ma, Victor E Reyes, Don W Powell, Irina V Pinchuk
Background and Aims: The role of programmed cell death protein 1 (PD-1) and its ligands in the dysregulation of T helper immune responses observed in the inflammatory bowel disease (IBD) is unclear. Recently, a novel concept emerged that CD90+ colonic (myo)fibroblasts (CMFs), also known as stromal cells, act as immunosuppressors, and are among the key regulators of acute and chronic inflammation. The objective of this study was to determine if the level of the PD-1 ligands is changed in the IBD inflamed colonic mucosa and to test the hypothesis that changes in IBD-CMF-mediated PD-1 ligand-linked immunosuppression is a mechanism promoting the dysregulation of Th1 cell responses...
2018: Frontiers in Immunology
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