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https://www.readbyqxmd.com/read/29241731/efficacy-of-lentiviral-mediated-gene-therapy-in-an-omenn-syndrome-rag2-mouse-model-is-not-hindered-by-inflammation-and-immune-dysregulation
#1
Valentina Capo, Maria Carmina Castiello, Elena Fontana, Sara Penna, Marita Bosticardo, Elena Draghici, Luigi P Poliani, Lucia Sergi Sergi, Rosita Rigoni, Barbara Cassani, Monica Zanussi, Paola Carrera, Paolo Uva, Kerry Dobbs, Nicolò Sacchetti, Luigi D Notarangelo, Niek P van Til, Gerard Wagemaker, Anna Villa
BACKGROUND: Omenn syndrome (OS) is a rare severe combined immunodeficiency associated with autoimmunity, caused by defects of the lymphoid-specific V(D)J recombination. Most patients carry hypomorphic mutations in recombination activating genes (RAG) 1 or 2. Hematopoietic stem cell (HSC) transplantation is the standard treatment, however gene therapy (GT) may represent a valid alternative, especially for patients lacking a matched donor. OBJECTIVE: To determine the efficacy of lentiviral vector (LV) mediated GT in the murine model of OS (Rag2R229Q/R229Q) in correcting immunodeficiency and autoimmunity...
December 11, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/29239188/-evaluation-of-inflammatory-cells-tumor-infiltrating-lymphocytes-in-solid-tumors
#2
P Dundr, K Němejcová, M Bártů, R Matěj, Z Rohan, I Tichá
BACKGROUND: The tumor microenvironment plays an important role in tumorigenesis and the tumor-host relationship. An important part of the tumor microenvironment is inflammatory infiltration. Its evaluation in solid tumors has prognostic meaning and appears also to be predictive of outcome, which is particularly important for predicting responses to immune checkpoint inhibitors. However, the methodology used to assess inflammatory infiltration is problematic, because it has been standardized only for certain types of tumors...
2017: Klinická Onkologie: Casopis Ceské a Slovenské Onkologické Spolecnosti
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
#3
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/29238163/the-coexpression-of-multi-immune-inhibitory-receptors-on-t-lymphocytes-in-primary-non-small-cell-lung-cancer
#4
REVIEW
Wenjie Guo, Sihan Liu, Xiaoli Zhang, Yating Chen, Ruolan Qian, Ziyuan Zou, Xin Chen, Peng Luo
Non-small-cell lung cancer (NSCLC) is a common disease threatening the health of humankind. It has a low survival rate and a poor prognosis. Under normal circumstances, tumor infiltrating lymphocytes (TILs) play the main role in the antitumor process, but studies in recent years have found that NSCLC is capable of releasing various immunosuppressive factors, inducing the TILs to exhibit high expression of immune inhibitory receptors and relevant immunosuppressive factors. They can not only activate their own signal pathways but also block those of TILs, which causes inefficiency of tumor destruction...
2017: Drug Design, Development 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
#5
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/29233559/tumour-infiltrating-lymphocytes-and-prognosis-in-different-subtypes-of-breast-cancer-a-pooled-analysis-of-3771-patients-treated-with-neoadjuvant-therapy
#6
Carsten Denkert, Gunter von Minckwitz, Silvia Darb-Esfahani, Bianca Lederer, Barbara I Heppner, Karsten E Weber, Jan Budczies, Jens Huober, Frederick Klauschen, Jenny Furlanetto, Wolfgang D Schmitt, Jens-Uwe Blohmer, Thomas Karn, Berit M Pfitzner, Sherko Kümmel, Knut Engels, Andreas Schneeweiss, Arndt Hartmann, Aurelia Noske, Peter A Fasching, Christian Jackisch, Marion van Mackelenbergh, Peter Sinn, Christian Schem, Claus Hanusch, Michael Untch, Sibylle Loibl
BACKGROUND: Tumour-infiltrating lymphocytes (TILs) are predictive for response to neoadjuvant chemotherapy in triple-negative breast cancer (TNBC) and HER2-positive breast cancer, but their role in luminal breast cancer and the effect of TILs on prognosis in all subtypes is less clear. Here, we assessed the relevance of TILs for chemotherapy response and prognosis in patients with TNBC, HER2-positive breast cancer, and luminal-HER2-negative breast cancer. METHODS: Patients with primary breast cancer who were treated with neoadjuvant combination chemotherapy were included from six randomised trials done by the German Breast Cancer Group...
December 7, 2017: Lancet Oncology
https://www.readbyqxmd.com/read/29232467/immunotherapy-in-ovarian-cancer
#7
K Odunsi
Immunological destruction of tumors is a multistep, coordinated process that can be modulated or targeted at several critical points to elicit tumor rejection. These steps in the cancer immunity cycle include: (i) generation of sufficient numbers of effector T cells with high avidity recognition of tumor antigens in vivo; (ii) trafficking and infiltration into the tumor; (iii) overcoming inhibitory networks in the tumor microenvironment; (iv) direct recognition of tumor antigens and generation of an effector anti-tumor response; and (v) persistence of the anti-tumor T cells...
November 1, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/29229854/interferon-beta-represses-cancer-stem-cell-properties-in-triple-negative-breast-cancer
#8
Mary R Doherty, HyeonJoo Cheon, Damian J Junk, Shaveta Vinayak, Vinay Varadan, Melinda L Telli, James M Ford, George R Stark, Mark W Jackson
Triple-negative breast cancer (TNBC), the deadliest form of this disease, lacks a targeted therapy. TNBC tumors that fail to respond to chemotherapy are characterized by a repressed IFN/signal transducer and activator of transcription (IFN/STAT) gene signature and are often enriched for cancer stem cells (CSCs). We have found that human mammary epithelial cells that undergo an epithelial-to-mesenchymal transition (EMT) following transformation acquire CSC properties. These mesenchymal/CSCs have a significantly repressed IFN/STAT gene expression signature and an enhanced ability to migrate and form tumor spheres...
December 11, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29229383/short-term-culture-with-il-2-is-beneficial-for-potent-memory-chimeric-antigen-receptor-t-cell-production
#9
Xuhua Zhang, Xiaodong Lv, Yongping Song
Interleukin-2 (IL-2) has been extensively used to boost the body's immune cells, especially T cells. IL-2 is a cytokine that for many years was used to activate and amplify T cells. Due to its potent T cell growth-inducing functions in vitro, for many years, IL-2 was used for the culture and expansion of various T cell products, including tumor-infiltrating lymphocytes (TIL), T cell receptors T cells (TCRT), or genetically engineered cells with chimeric antigen receptors T cells (CAR T). Despite its positive effect on T cell production, the side-effect is not well studied...
December 8, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29225479/density-of-cd8-lymphocytes-in-biopsy-samples-combined-with-the-circulating-lymphocyte-ratio-predicts-pathologic-complete-response-to-chemoradiotherapy-for-rectal-cancer
#10
Binyi Xiao, Jianhong Peng, Rongxin Zhang, Jing Xu, Yongchun Wang, Yujing Fang, Junzhong Lin, Zhizhong Pan, Xiaojun Wu
Objectives: The systemic status and local immune status, as determined by the neutrophil-lymphocyte ratio (NLR) or the lymphocyte ratio (LYMR) and tumor-infiltrating lymphocyte (TIL) count, respectively, have been suggested as predictors of the tumor response to neoadjuvant chemoradiotherapy (nCRT) in rectal cancer, although the utility of these measures remains controversial. We aimed to investigate the values of the LYMR, NLR and TIL count and their combinations (TIL-LYMR/TIL-NLR) in predicting pathologic complete response (pCR) after nCRT...
2017: Cancer Management and Research
https://www.readbyqxmd.com/read/29222623/tumor-infiltrating-lymphocytes-in-breast-cancer-patients-with-progressive-disease-during-neoadjuvant-chemotherapy
#11
Jacques Raphael, S Nofech-Mozes, T Paramsothy, N Li, S Gandhi
A minority of breast cancer (BC) patients progress during neoadjuvant chemotherapy (NCT). The aim of this study was to assess the value of Tumor infiltrating lymphocytes (TILs) in such a high-risk population where valid biomarkers are eagerly needed. A retrospective review identified BC patients who either progressed during NCT or achieved a pathologic complete response (pCR). An experienced BC pathologist semi-quantified stromal TILs in pre-treatment core biopsies using hematoxylin and eosin stained slides...
December 8, 2017: Pathology Oncology Research: POR
https://www.readbyqxmd.com/read/29206673/pd-l1-expression-tumor-infiltrating-lymphocytes-and-clinical-outcome-in-patients-with-surgically-resected-esophageal-cancer
#12
Taisuke Yagi, Yoshifumi Baba, Takatsugu Ishimoto, Masaaki Iwatsuki, Yuji Miyamoto, Naoya Yoshida, Masayuki Watanabe, Hideo Baba
OBJECTIVES: To examine the prognostic impact of the programmed death ligand 1 (PD-L1) expression, tumor-infiltrating lymphocyte (TIL) status, and their combination in esophageal cancer. SUMMARY BACKGROUND DATA: PD-L1 has garnered much attention for its roles in tumor immunology and as an immune-based therapeutic target. To ensure a response to PD-L1 checkpoint inhibitor, a new framework based on PD-L1 expression and the presence or absence of TILs is required. METHODS: Using a nonbiased database of 305 curatively resected esophageal cancers, we evaluated PD-L1 expression and TIL status (cluster of differentiation 8 (CD8) expression) by immunohistochemical analysis...
December 4, 2017: Annals of Surgery
https://www.readbyqxmd.com/read/29203588/spatially-resolved-and-quantitative-analysis-of-vista-pd-1h-as-a-novel-immunotherapy-target-in-human-non-small-cell-lung-cancer
#13
Franz Villarroel-Espindola, Xiaoqing Yu, Ila Datar, Nikita Mani, Miguel F Sanmamed, Vamsidhar Velcheti, Konstantinos N Syrigos, Maria I Toki, Hongyu Zhao, Lieping Chen, Roy S Herbst, Kurt A Schalper
PURPOSE: Determine the localized expression pattern and clinical significance of VISTA/PD-1H in human NSCLC. EXPERIMENTAL DESIGN: Using multiplex quantitative immunofluorescence (QIF), we performed localized measurements of VISTA, PD-1 and PD-L1 protein in 758 stage I-IV NSCLCs from 3 independent cohorts represented in tissue microarray format. The targets were selectively measured in cytokeratin+ tumor epithelial cells, CD3+ T-cells, CD4+ T-helper cells, CD8+ cytotoxic T-cells, CD20+ B-lymphocytes and CD68+ tumor-associated macrophages...
December 4, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29202885/the-command-trial-of-cognitive-therapy-to-prevent-harmful-compliance-with-command-hallucinations-predictors-of-outcome-and-mediators-of-change
#14
Max Birchwood, Graham Dunn, Alan Meaden, Nicholas Tarrier, Shon Lewis, Til Wykes, Linda Davies, Maria Michail, Emmanuelle Peters
BACKGROUND: Acting on harmful command hallucinations is a major clinical concern. Our COMMAND CBT trial approximately halved the rate of harmful compliance (OR = 0.45, 95% CI 0.23-0.88, p = 0.021). The focus of the therapy was a single mechanism, the power dimension of voice appraisal, was also significantly reduced. We hypothesised that voice power differential (between voice and voice hearer) was the mediator of the treatment effect. METHODS: The trial sample (n = 197) was used...
December 5, 2017: Psychological Medicine
https://www.readbyqxmd.com/read/29200891/conditioning-on-future-exposure-to-define-study-cohorts-can-induce-bias-the-case-of-low-dose-acetylsalicylic-acid-and-risk-of-major-bleeding
#15
Jennifer L Lund, Erzsébet Horváth-Puhó, Szimonetta Komjáthiné Szépligeti, Henrik Toft Sørensen, Lars Pedersen, Vera Ehrenstein, Til Stürmer
Background: A principle of cohort studies is that cohort membership is defined by current rather than future exposure information. Pharmacoepidemiologic studies using existing databases are vulnerable to violation of this principle. We evaluated the impact of using data on future redemption of prescriptions to determine cohort membership, motivated by a published example seeking to emulate a "per-protocol" association between continuous versus never use of low-dose acetylsalicylic acid (ASA) and major bleeding (e...
2017: Clinical Epidemiology
https://www.readbyqxmd.com/read/29198959/evaluation-of-immune-reaction-and-pd-l1-expression-using-multiplex-immunohistochemistry-in-her2-positive-breast-cancer-the-association-with-response-to-anti-her2-neoadjuvant-therapy
#16
Yanjun Hou, Hiroaki Nitta, Lai Wei, Peter M Banks, Anil V Parwani, Zaibo Li
BACKGROUND: Immune reaction with tumor-infiltrating lymphocytes (TILs) has been extensively investigated in breast cancer. Programmed cell death 1 and its ligand (PD-L1) are key physiologic suppressors of cytotoxic immune reaction. However, the combination of TILs with PD-L1 expression has not been well studied in breast cancer. PATIENTS AND METHODS: A multi-color immunohistochemical multiplex assay simultaneously detecting PD-L1, CD8, and CD163 was performed on biopsy whole sections from 123 HER2-positive (HER2+) breast cancers, including 64 treated with anti-HER2 neoadjuvant therapy and subsequent resection...
November 9, 2017: Clinical Breast Cancer
https://www.readbyqxmd.com/read/29197404/integrated-mental-health-care-and-vocational-rehabilitation-to-improve-return-to-work-rates-for-people-on-sick-leave-because-of-exhaustion-disorder-adjustment-disorder-and-distress-the-danish-ibbis-trial-study-protocol-for-a-randomized-controlled-trial
#17
Rie Poulsen, Jonas Fisker, Andreas Hoff, Carsten Hjorthøj, Lene Falgaard Eplov
BACKGROUND: Common mental disorders are important contributors to the global burden of disease and cause negative effects on both the individual and society. Stress-related disorders influence the individual's workability and cause early retirement pensions in Denmark. There is no clear evidence that mental health care alone will provide sufficient support for vocational recovery for this group. Integrated vocational and health care services have shown good effects on return to work in other similar welfare contexts...
December 2, 2017: Trials
https://www.readbyqxmd.com/read/29191604/mhc-class-ii-expression-in-lung-cancer
#18
Yayi He, Leslie Rozeboom, Christopher J Rivard, Kim Ellison, Rafal Dziadziuszko, Hui Yu, Caicun Zhou, Fred R Hirsch
BACKGROUND: Immunotherapy is an exciting development in lung cancer research. In this study we described major histocompatibility complex (MHC) Class II protein expression in lung cancer cell lines and patient tissues. METHODS: We studied MHC Class II (DP, DQ, DR) (CR3/43, Abcam) protein expression in 55 non-small cell lung cancer (NSCLC) cell lines, 42 small cell lung cancer (SCLC) cell lines and 278 lung cancer patient tissues by immunohistochemistry (IHC). RESULTS: Seven (12...
October 2017: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/29190949/association-between-pd-l1-expression-combined-with-tumor-infiltrating-lymphocytes-and-the-prognosis-of-patients-with-advanced-hypopharyngeal-squamous-cell-carcinoma
#19
Takeharu Ono, Koichi Azuma, Akihiko Kawahara, Tetsuro Sasada, Satoshi Hattori, Fumihiko Sato, Buichiro Shin, Shun-Ich Chitose, Jun Akiba, Umeno Hirohito
Limited information is available regarding the immune-related prognostic factors of patients with advanced hypopharyngeal squamous cell carcinoma (HPSCC). The expression of programmed cell death-ligand 1 (PD-L1) in tumor cells contributes to a mechanism that allows cancer cells to escape immune surveillance. We investigated whether PD-L1 or human leukocyte antigen (HLA) class I expression in tumor cells and the tumor-infiltrating lymphocyte (TIL) density were associated with the tumor response to neoadjuvant chemotherapy (NAC) and survival in patients with advanced HPSCC...
November 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/29189259/histologic-features-do-not-reliably-predict-mismatch-repair-protein-deficiency-in-colorectal-carcinoma-the-results-of-a-5-year-prospective-evaluation
#20
Dane C Olevian, Reetesh K Pai
Most major professional medical organizations advocate universal screening for Lynch syndrome in colorectal carcinoma; however, some allow for a selective screening approach based on clinicopathologic factors including assessment of histologic features of mismatch repair protein deficiency (MMRD). We performed a prospective evaluation for histopathologic features of MMRD in colorectal carcinomas that underwent universal screening for Lynch syndrome to evaluate the ability of histology to predict MMRD. In total, 947 resected colorectal carcinomas over a 5-year period were prospectively analyzed for histologic features of MMRD and for DNA mismatch repair protein abnormalities...
November 20, 2017: Applied Immunohistochemistry & Molecular Morphology: AIMM
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