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https://www.readbyqxmd.com/read/29245183/increased-expression-and-modulated-regulatory-activity-of-co-inhibitory-receptors-pd-1-tigit-and-tim-3-in-lymphocytes-of-systemic-sclerosis-patients
#1
Michelle Fleury, Anna C Belkina, Elizabeth A Proctor, Christopher Zammitti, Robert W Simms, Douglas A Lauffenburger, Jennifer E Snyder-Cappione, Robert Lafyatis, Hans Dooms
OBJECTIVE: Immune dysfunction is an important component of the disease process underlying Systemic Sclerosis (SSc), but the mechanisms contributing to altered immune cell function in SSc remain poorly defined. Here, we measured the expression and function of the co-inhibitory receptors (co-IRs) PD-1, TIGIT, TIM-3, and LAG-3 in lymphocyte subsets from the peripheral blood of SSc patients. METHODS: Co-IR expression levels on immune cell subsets were analyzed using a 16-color flow cytometry panel...
December 15, 2017: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/29243219/pd-1-blockade-enhances-the-anti-tumor-efficacy-of-gm-csf-surface-modified-bladder-cancer-stem-cells-vaccine
#2
Xiaojun Shi, Xinji Zhang, Jinlong Li, Lijun Mo, Hongfan Zhao, Yongtong Zhu, Zhiming Hu, Jimin Gao, Wanlong Tan
Eliminating cancer stem cells (CSCs) is a key issue in eradicating tumor. The streptavidin-granulocyte -macrophage colony stimulating factor (SA-GM-CSF) surface-modified bladder cancer stem cells vaccine previously developed using our protein-anchor technology could effectively induce specific immune response for eliminating CSCs. However, program death receptor-1 (PD-1)/program death ligand 1 (PD-L1) signaling in tumor microenvironment results in tumor adaptive immune resistance. Although the CSCs vaccine could increase the number of CD8+ T-cells, a part of these CD8+ T-cells expressed PD-1...
December 15, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/29241377/current-and-future-immunotherapies-for-thyroid-cancer
#3
Alessandro Antonelli, Silvia Martina Ferrari, Poupak Fallahi
Cancer immunotherapies were approved in recent years, including immune checkpoint inhibitors. Experience with ipilimumab (CTLA-4 antagonist), nivolumab and pembrolizumab (PD-1 antagonists), and atezolizumab (PD-L1 antagonist) has shown that the impact on overall survival in cancer patients is paramount. Immune checkpoint inhibitors target the immune system and they can be applied across multiple cancers; the response rate is ranging from 20 to 40%. Many studies have shown that thyroid cancer (TC) cells produce cytokines and chemokines, inducing several tumor-promoting effects...
December 15, 2017: Expert Review of Anticancer Therapy
https://www.readbyqxmd.com/read/29239194/-immunotherapy-of-renal-cell-carcinoma
#4
A Poprach, R Lakomý, T Büchler
Treatment of renal cell carcinoma is still palliative. Targeted therapy increases response rates and prolongs overall survival and progression-free survival compared with cytokines and chemotherapy. Checkpoint inhibitors constitute the up-date of therapeutic approaches, and anti-PD-1 antibody, one checkpoint inhibitor, is now well established as a second and/or third palliative treatment for patients with renal cell carcinoma. In this study, we present the latest data from current studies on cytokines, cancer vaccines, ipilimumab, and nivolumab...
2017: Klinická Onkologie: Casopis Ceské a Slovenské Onkologické Spolecnosti
https://www.readbyqxmd.com/read/29238906/thyroid-dysfunctions-secondary-to-cancer-immunotherapy
#5
REVIEW
P Chalan, G Di Dalmazi, F Pani, A De Remigis, A Corsello, P Caturegli
BACKGROUND: Immunotherapy is a firmly established pillar in the treatment of cancer, alongside the traditional approaches of surgery, radiotherapy, and chemotherapy. Like every treatment, also cancer immunotherapy causes a diverse spectrum of side effects, collectively referred to as immune-related adverse events. OBJECTIVE: This review will examine the main forms of immunotherapy, the proposed mechanism(s) of action, and the incidence of thyroid dysfunctions. METHODS: A comprehensive MEDLINE search was performed for articles published up to March 30, 2017...
December 13, 2017: Journal of Endocrinological Investigation
https://www.readbyqxmd.com/read/29238224/prognostic-value-of-cox-2-and-pd-l1-expression-and-its-relationship-with-tumor-infiltrating-lymphocytes-in-resected-lung-adenocarcinoma
#6
Katsuhiko Shimizu, Riki Okita, Shinsuke Saisho, Ai Maeda, Yuji Nojima, Masao Nakata
Programmed cell death-1 ligand 1 (PD-L1), tumor-infiltrating CD8-positive T lymphocytes (CD8-positive TILs), and cyclooxygenase-2 (Cox-2) have been used as prognostic tools in patients with lung adenocarcinoma. We conducted a retrospective review of data from 170 patients who had undergone pulmonary resection as an initial treatment for clinical T1-2 N0 lung adenocarcinoma. We then investigated the expressions of three biomarkers using immunohistochemical analyses and compared the expression levels with the clinicopathological characteristics and outcomes of the patients...
2017: Cancer Management and Research
https://www.readbyqxmd.com/read/29238207/advances-in-t-cell-checkpoint-immunotherapy-for-head-and-neck-squamous-cell-carcinoma
#7
REVIEW
Xinmeng Qi, Bo Jia, Xue Zhao, Dan Yu
Head and neck squamous cell carcinoma (HNSCC) has been found to be a complex group of malignancies characterized by their profound immunosuppression and high aggressiveness. In most cases of advanced HNSCC, treatment fails to obtain total cancer cure. Efforts are needed to develop new therapeutic approaches to improve HNSCC outcomes. In this light, T-cells "immune checkpoint" has attracted much attention in cancer immunotherapy. It has been broadly accepted that inhibitory T-cell immune checkpoints contribute to tumor immune escape through negative immune regulatory signals (cytotoxic T-lymphocyte-associated antigen 4 [CTLA-4], programmed cell death 1 [PD-1], B7-H3, and B7-H4, etc)...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/29237087/type-frequency-and-spatial-distribution-of-immune-cell-infiltrates-in-cns-germinomas-evidence-for-inflammatory-and-immunosuppressive-mechanisms
#8
Pia Zapka, Evelyn Dörner, Verena Dreschmann, Noriaki Sakamato, Glen Kristiansen, Gabriele Calaminus, Christian Vokuhl, Ivo Leuschner, Torsten Pietsch
Central nervous system germinomas are characterized by a massive immune cell infiltrate. We systematically characterized these immune cells in 28 germinomas by immunophenotyping and image analysis. mRNA expression was analyzed by Nanostring technology and in situ RNA hybridization. Tumor infiltrating lymphocytes (TILs) were composed of 61.8% ± 3.1% (mean ± SE) CD3-positive T cells, including 45.2% ± 3.5% of CD4-positive T-helper cells, 23.4% ± 1.5% of CD8-positive cytotoxic T cells, 5.5% ± 0...
December 11, 2017: Journal of Neuropathology and Experimental Neurology
https://www.readbyqxmd.com/read/29236302/recovery-of-hepatitis-c-specific-t-cell-responses-after-rituximab-therapy-in-hepatitis-c-mixed-cryoglobulinemic-vasculitis
#9
Poonam Mathur, Benjamin Emmanuel, Michael Sneller, Xiaozhen Zhang, Bhawna Poonia, Shyamasundaran Kottilil
BACKGROUND & AIMS: Mixed cryoglobulinemic vasculitis is associated with monoclonal B cell expansion in patients with chronic hepatitis C (HCV) infection. B cell depletion therapy using rituximab, a CD20 monoclonal antibody, has been successful in achieving remission from symptomatic disease. This study investigated whether B cell depletion therapy has an impact on activation of HCV-specific T cell phenotype and function. METHODS: Nineteen patients with Hepatitis C mixed cryoglobulinemic vasculitis were treated with 4 cycles of rituximab (375mg/m2 ) and variables were measured 6 months after therapy...
December 13, 2017: Journal of Medical Virology
https://www.readbyqxmd.com/read/29234685/local-and-systemic-cd4-t-cell-exhaustion-reverses-with-clinical-resolution-of-pulmonary-sarcoidosis
#10
Charlene Hawkins, Guzel Shaginurova, D Auriel Shelton, Jose D Herazo-Maya, Kyra A Oswald-Richter, Joseph E Rotsinger, Anjuli Young, Lindsay J Celada, Naftali Kaminski, Carla Sevin, Wonder P Drake
Investigation of the Th1 immune response in sarcoidosis CD4+ T cells has revealed reduced proliferative capacity and cytokine expression upon TCR stimulation. In other disease models, such cellular dysfunction has been associated with a step-wise, progressive loss of T cell function that results from chronic antigenic stimulation. T cell exhaustion is defined by decreased cytokine production upon TCR activation, decreased proliferation, increased expression of inhibitory cell surface receptors, and increased susceptibility to apoptosis...
2017: Journal of Immunology Research
https://www.readbyqxmd.com/read/29233904/autologous-dendritic-cells-pulsed-with-allogeneic-tumor-cell-lysate-in-mesothelioma-from-mouse-to-human
#11
Joachim G Aerts, Pauline L de Goeje, Robin Cornelissen, Margaretha E H Kaijen-Lambers, Koen Bezemer, Cor van der Leest, Niken M Mahaweni, Andre Kunert, Ferry A L M Eskens, Cynthia Waasdorp, Eric Braakman, Bronno van der Holt, Arnold G Vulto, Rudi W Hendriks, Joost P J J Hegmans, Henk C Hoogsteden
PURPOSE: Mesothelioma has been regarded as a non-immunogenic tumor, which is also shown by the low response rates to treatments targeting the PD-1/PD-L1 axis.  Previously, we demonstrated that autologous tumor lysate-pulsed dendritic cell (DC) immunotherapy increased T-cell response towards malignant mesothelioma. However, the use of autologous tumor material hampers implementation in large clinical trials, which might be overcome by using allogeneic tumor cell lines as tumor antigen source...
December 12, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29233903/clinical-significance-of-pd-l1-exosomes-in-plasma-of-head-and-neck-cancer-patients
#12
Marie-Nicole Theodoraki, Saigopalakrishna Yerneni, Thomas K Hoffmann, William E Gooding, Theresa L Whiteside
PURPOSE: The microenvironment of head and neck squamous cell carcinomas (HNSCCs) is highly immunosuppressive. HNSCCs expressing elevated levels of PD-L1 have especially poor outcome. Exosomes that carry PD-L1 and suppress T-cell functions have been isolated from plasma of patients with HNSCC. The potential contributions of PD-L1+ exosomes to immune suppression and disease activity are evaluated. METHODS: Exosomes isolated from plasma of 40 HNSCC patients by size exclusion chromatography were captured on beads using anti-CD63 Abs, stained for PD-1 and PD-L1 and analyzed by flow cytometry...
December 12, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29233542/natural-killer-cells-and-anti-tumor-immunity
#13
Sandra E Nicholson, Narelle Keating, Gabrielle T Belz
Immune checkpoint inhibitors harness the power of the immune system to fight cancer. The clinical success achieved with antibodies against the inhibitory T cell receptors PD-1 and CTLA4 has focused attention on the possibility of manipulating other immune cells, in particular those involved in innate immunity. Here we review the role of innate lymphoid cells (ILCs) and their contribution to tumor immunity. As the prototypical ILC, the natural killer (NK) cell has an intrinsic ability to detect and kill cancer cells...
December 9, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/29232699/cxcr4-blockade-decreases-cd4-t-cell-exhaustion-and-improves-survival-in-a-murine-model-of-polymicrobial-sepsis
#14
Kimberly M Ramonell, Wenxiao Zhang, Annette Hadley, Ching-Wen Chen, Katherine T Fay, John D Lyons, Nathan J Klingensmith, Kevin W McConnell, Craig M Coopersmith, Mandy L Ford
Sepsis is a dysregulated systemic response to infection involving many inflammatory pathways and the induction of counter-regulatory anti-inflammatory processes that results in a state of immune incompetence and can lead to multi-organ failure. CXCR4 is a chemokine receptor that, following ligation by CXCL12, directs cells to bone marrow niches and also plays an important role in T cell cosignaling and formation of the immunological synapse. Here, we investigated the expression and function of CXCR4 in a murine model of polymicrobial sepsis...
2017: PloS One
https://www.readbyqxmd.com/read/29228688/altered-follicular-helper-t-cell-impaired-antibody-production-in-a-murine-model-of-myelodysplastic-syndromes
#15
Huijuan Jiang, Ningbo Cui, Liyan Yang, Chunyan Liu, Lanzhu Yue, Lifang Guo, Huaquan Wang, Zonghong Shao
Myelodysplastic syndromes (MDS) are a group of clonal hematopoietic diseases which have a high risk of progressing to acute myeloid leukemia. MDS patients have immunologic deficiency, including T and B cells dysfunction. Follicular T helper cells (Tfh, CD4+CXCR5+) are an important subset of helper T cells which help to the formation of germinal centers and B cells differentiation. In this study, we investigated the proportion and function of Tfh using NUP98-HOXD13 transgenic (NHD13) mice model with MDS phenotype...
November 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29228684/atorvastatin-downregulates-co-inhibitory-receptor-expression-by-targeting-ras-activated-mtor-signalling
#16
Isobel Okoye, Afshin Namdar, Lai Xu, Nicole Crux, Shokrollah Elahi
Regulation of T cell function in the steady state is mediated by co-inhibitory receptors or immune checkpoints such as PD-1, CTLA-4, TIM-3 and LAG-3. Persistent antigen stimulation, during chronic viral infections and cancer, results in sustained expression of multiple co-inhibitory receptors and subsequently poor effector T cell function. Immune checkpoint blockade using monoclonal antibodies against PD-1, PDL-1 and CTLA-4 has been implemented as an immunotherapy strategy- resulting in restoration of T cell function and reduction of viral load or tumour growth...
November 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29228642/soluble-pd-1-and-pd-l1-predictive-and-prognostic-significance-in-cancer
#17
REVIEW
Xinxin Zhu, Jinghe Lang
The membrane-bound molecules programmed death 1 (PD-1) and its ligand PD-L1 (PD-1/PD-L1) belong to the immune checkpoint pathway. PD-1 pathway downregulates effector T cells in immune response, thereby causing immune suppression. Recent studies have revealed that membrane-bound PD-1 and PD-L1 also have soluble forms. These soluble forms increase the complexity and diversity of the composition and function of the PD-1/PD-L1 signaling pathway. However, the exact roles of these molecules remain unknown. The objective of this systematic review was to elucidate the biological significance of soluble PD-1/PD-L1 in human cancers and evaluate whether they are potential diagnostic, therapeutic, or prognostic biomarkers...
November 14, 2017: Oncotarget
https://www.readbyqxmd.com/read/29222312/harnessing-the-power-of-the-immune-system-in-non-hodgkin-lymphoma-immunomodulators-checkpoint-inhibitors-and-beyond
#18
REVIEW
Stephen M Ansell
Non-Hodgkin lymphoma is a malignancy of B lymphocytes that typically infiltrate sites of disease, including the lymph nodes, spleen, and bone marrow. Beyond the presence of malignant cells, many immune cells are also present within the tumor microenvironment. Although these immune cells have the potential to regulate the growth of malignant B cells, intratumoral immune cells are unable to eradicate lymphoma cells and most patients with lymphoma have clinical evidence of disease progression. Recent data have identified some of the mechanisms that account for the suppressed antitumor immune response and have created opportunities for treatment to overcome the deficiencies...
December 8, 2017: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/29221730/ablation-of-transcription-factor-irf4-promotes-transplant-acceptance-by-driving-allogenic-cd4-t-cell-dysfunction
#19
Jie Wu, Hedong Zhang, Xiaomin Shi, Xiang Xiao, Yihui Fan, Laurie J Minze, Jin Wang, Rafik M Ghobrial, Jiahong Xia, Roger Sciammas, Xian C Li, Wenhao Chen
CD4+ T cells orchestrate immune responses and destruction of allogeneic organ transplants, but how this process is regulated on a transcriptional level remains unclear. Here, we demonstrated that interferon regulatory factor 4 (IRF4) was a key transcriptional determinant controlling T cell responses during transplantation. IRF4 deletion in mice resulted in progressive establishment of CD4+ T cell dysfunction and long-term allograft survival. Mechanistically, IRF4 repressed PD-1, Helios, and other molecules associated with T cell dysfunction...
December 4, 2017: Immunity
https://www.readbyqxmd.com/read/29221649/-two-cases-of-granuloma-annulare-under-anti-pd1-therapy
#20
R Charollais, F Aubin, B Roche-Kubler, E Puzenat
BACKGROUND: Granuloma annulare as a granulomatous cutaneous reaction may be drug-induced. Immune checkpoint inhibitors including programmed death-1 (PD-1) inhibitors show remarkable antitumor activity and are approved for melanoma and other cancers. Different immune-related adverse effects have been described. We report herein a rare adverse effect of anti-PD1 therapy given for metastatic melanoma : granuloma annulare. PATIENTS AND METHODS: Two women receiving pembrolizumab metastatic melanoma presented with granuloma annulare...
December 5, 2017: Annales de Dermatologie et de Vénéréologie
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