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https://www.readbyqxmd.com/read/29784674/clinically-relevant-cytotoxic-immune-cell-signatures-and-clonal-expansion-of-t-cell-receptors-in-high-risk-mycn-not-amplified-human-neuroblastoma
#1
Jun S Wei, Igor B Kuznetsov, Shile Zhang, Young K Song, Shahab Asgharzadeh, Sivasish Sindiri, Xinyu Wen, Rajesh Patidar, Sushma Nagaraj, Ashley Walton, Jaime M Guidry Auvil, Daniela S Gerhard, Aysen Yuksel, Daniel R Catchpoole, Stephen M Hewitt, Paul M Sondel, Robert C Seeger, John M Maris, Javed Khan
PURPOSE: High-risk neuroblastoma is an aggressive disease. DNA sequencing studies have revealed a paucity of actionable genomic alterations and a low mutation burden, posing challenges to develop effective novel therapies. We used RNA sequencing (RNA-seq) to investigate the biology of this disease including a focus on tumor-infiltrating lymphocytes (TILs). EXPERIMENTAL DESIGN: We performed deep RNA-seq on pre-treatment diagnostic tumors from 129 high-risk and 21 low- or intermediate-risk patients with neuroblastomas...
May 21, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29784242/hearing-outcomes-of-the-active-bone-conduction-system-bonebridge-%C3%A2-in-conductive-or-mixed-hearing-loss
#2
Claudio Carnevale, Guillermo Til-Pérez, Diego J Arancibia-Tagle, Manuel D Tomás-Barberán, Pedro L Sarría-Echegaray
OBJECTIVE: The active transcutaneous bone conduction implant Bonebridge® , is indicated for patients affected by bilateral conductive/mixed hearing loss or unilateral sensorineural hearing loss, showing hearing outcomes similar to other percutaneous bone conduction implants, but with a lower rate of complications. The aim of this study was to analyze the hearing outcomes in a series of 26 patients affected by conductive or mixed hearing loss and treated with Bonebridge® . METHODS: 26 of 30 patients implanted with Bonebridge® between October 2012 and May 2017, were included in the study...
May 18, 2018: Acta Otorrinolaringológica Española
https://www.readbyqxmd.com/read/29781773/a-comparison-of-total-inward-leakage-measured-using-sodium-chloride-nacl-and-corn-oil-aerosol-methods-for-air-purifying-respirators
#3
Samy Rengasamy, Ziqing Zhuang, George Niezgoda, Gary Walbert, Robert Lawrence, Brenda Boutin, Judith Hudnall, William P Monaghan, Michael Bergman, Colleen Miller, James Harris, Christopher Coffey
The International Organization for Standardization (ISO) standard 16900-1:2014 specifies the use of sodium chloride (NaCl) and corn oil aerosols, and sulfur hexafluoride gas for measuring total inward leakage (TIL). However, a comparison of TIL between different agents is lacking. The objective of this study was to measure and compare TIL for respirators using corn oil and NaCl aerosols. TIL was measured with 10 subjects donning two models of filtering facepiece respirators (FFRs) including FFP1, N95, P100, and elastomeric half-mask respirators (ERs) in NaCl and corn oil aerosol test chambers, using continuous sampling methods...
May 21, 2018: Journal of Occupational and Environmental Hygiene
https://www.readbyqxmd.com/read/29770915/cytolytic-activity-score-to-assess-anticancer-immunity-in-colorectal-cancer
#4
Sumana Narayanan, Tsutomu Kawaguchi, Li Yan, Xuan Peng, Qianya Qi, Kazuaki Takabe
BACKGROUND: Elevated tumor-infiltrating lymphocytes (TILs) within the tumor microenvironment is a known positive prognostic factor in colorectal cancer (CRC). We hypothesized that since cytotoxic T cells release cytolytic proteins such as perforin (PRF1) and pro-apoptotic granzymes (GZMA) to attack cancer cells, a cytolytic activity score (CYT) would be a useful tool to assess anticancer immunity. METHODS: Genomic expression data were obtained from 456 patients from The Cancer Genome Atlas (TCGA)...
May 16, 2018: Annals of Surgical Oncology
https://www.readbyqxmd.com/read/29769722/bystander-cd8-t-cells-are-abundant-and-phenotypically-distinct-in-human-tumour-infiltrates
#5
Yannick Simoni, Etienne Becht, Michael Fehlings, Chiew Yee Loh, Si-Lin Koo, Karen Wei Weng Teng, Joe Poh Sheng Yeong, Rahul Nahar, Tong Zhang, Hassen Kared, Kaibo Duan, Nicholas Ang, Michael Poidinger, Yin Yeng Lee, Anis Larbi, Alexis J Khng, Emile Tan, Cherylin Fu, Ronnie Mathew, Melissa Teo, Wan Teck Lim, Chee Keong Toh, Boon-Hean Ong, Tina Koh, Axel M Hillmer, Angela Takano, Tony Kiat Hon Lim, Eng Huat Tan, Weiwei Zhai, Daniel S W Tan, Iain Beehuat Tan, Evan W Newell
Various forms of immunotherapy, such as checkpoint blockade immunotherapy, are proving to be effective at restoring T cell-mediated immune responses that can lead to marked and sustained clinical responses, but only in some patients and cancer types1-4 . Patients and tumours may respond unpredictably to immunotherapy partly owing to heterogeneity of the immune composition and phenotypic profiles of tumour-infiltrating lymphocytes (TILs) within individual tumours and between patients5,6 . Although there is evidence that tumour-mutation-derived neoantigen-specific T cells play a role in tumour control2,4,7-10 , in most cases the antigen specificities of phenotypically diverse tumour-infiltrating T cells are largely unknown...
May 16, 2018: Nature
https://www.readbyqxmd.com/read/29768723/importance-of-choice-of-materials-and-methods-in-pd-l1-and-til-assessment-in-oropharyngeal-squamous-cell-carcinoma
#6
Astrid De Meulenaere, Tijl Vermassen, David Creytens, Sandrine Aspeslagh, Philippe Deron, Frederic Duprez, Sylvie Rottey, Jo Van Dorpe, Liesbeth Ferdinande
INTRODUCTION: A great deal of research is being conducted into PD-L1 immunohistochemistry (IHC) and tumor infiltrating lymphocytes (TILs) as predictive or prognostic biomarkers for immunotherapy, although several practical issues exist concerning their assessment. The aim of this research was therefore to assess the importance of choice of materials and methods in PD-L1 and TILs scoring in oropharyngeal squamous cell carcinoma (OSCC). METHODS AND RESULTS: IHC for PD-L1 (SP142 and 22C3 clone) and TILs subtyping was performed on formalin-fixed paraffin-embedded tissue slides (biopsy, resection and/or lymph nodes specimens) of 99 patients with OSCC...
May 16, 2018: Histopathology
https://www.readbyqxmd.com/read/29766362/exploration-of-tumour-infiltrating-lymphocytes-as-a-predictive-biomarker-for-adjuvant-endocrine-therapy-in-early-breast-cancer
#7
Erik J Blok, Charla C Engels, Geeske Dekker-Ensink, Elma Meershoek-Klein Kranenbarg, Hein Putter, Vincent T H B M Smit, Gerrit-Jan Liefers, James P Morden, Judith M Bliss, R Charles Coombes, John M S Bartlett, Judith R Kroep, Cornelis J H van de Velde, Peter J K Kuppen
PURPOSE: Tumour-infiltrating lymphocytes (TILs) have been shown to be prognostic for disease-free survival and predictive for the benefit of chemotherapy in patients with early breast cancer, but have not been studied for endocrine therapy. EXPERIMENTAL DESIGN: The number of CD8-positive TILs was assessed in a subcohort of 236 patients in the Intergroup Exemestane Study. AQ After 2-3 years of adjuvant tamoxifen, AQpatients were randomized between the schemes of continuation for 5 years on tamoxifen and switching to exemestane...
May 15, 2018: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/29765252/triple-negative-and-her2-overexpressing-breast-cancer-cell-sialylation-impacts-tumor-microenvironment-t-lymphocyte-subset-recruitment-a-possible-mechanism-of-tumor-escape
#8
Christian Garbar, Corinne Mascaux, Yacine Merrouche, Armand Bensussan
Introduction: Breast cancers develop different patterns of sialylation to modulate their tumor-infiltrating lymphocyte (TIL) environment. We studied the relationship between α-2,6 sialyltransferases and the TIL in different breast cancer molecular subgroups. Materials and methods: Immunohistochemical preparations were made from 39 luminal (LUM), 13 human epidermal growth factor receptor 2-overexpressing (HER2) and 47 triple-negative (TN) breast carcinomas. Targeted proteins included ST6Gal-I, ST6Gal-II, ST6GalNac-I, CD8, CD4 and granzyme-B in both cytotoxic T lymphocytes and NK lymphocytes (CTL/NK)...
2018: Cancer Management and Research
https://www.readbyqxmd.com/read/29764038/-expression-and-distribution-of-programmed-death-receptor-1-and-t-cell-immunoglobulin-mucin-3-in-breast-cancer-microenvironment-and-its-relationship-with-clinicopathological-features
#9
H Shen, H Sheng, J J Lu, C Feng, M Yao, H Pan, L S Xu, J F Shen, Y Zheng, Y L Zhou
Objective: To explore the expression and distribution of programmed death receptor 1 (PD-1) and T-cell immunoglobulin mucin 3 (TIM-3) in breast cancer microenvironment and analyze the their correlation with the clinicopathological features. Methods: The specimens of tumor tissue and adjacent tissues from 30 patients with infiltrative breast cancer who were diagnosed as breast cancer from June 2016 to May 2017 in The First Hospital of Jiaxing were collected, and the specimen were divided into two parts along the center...
May 8, 2018: Zhonghua Yi Xue za Zhi [Chinese medical journal]
https://www.readbyqxmd.com/read/29762449/time-to-procedure-nuclear-imaging-and-clinicopathological-characteristics-as-predictive-factors-for-sentinel-lymph-node-metastasis-in-cutaneous-melanoma-a-single-center-analysis
#10
Ljiljana Jaukovic, Milica Rajović, Lidija Kandolf Sekulovic, Marija Radulovic, Nenad Stepic, Zeljko Mijuskovic, Nenad Petrov, Boris Ajdinovic
OBJECTIVE: Sentinel lymph node (SLN) biopsy is a widely accepted staging procedure for cutaneous melanoma patients who are at risk of clinically occult nodal metastases. Numerous predictive factors for regional lymph node metastases have been identified; however, few have been found to be reproducibly significant. Also, the role of blue dye in identification was questioned in recent trials. Time to procedure was also found to be predictive of SLN positivity, but this was not confirmed in other studies...
May 14, 2018: Annals of Plastic Surgery
https://www.readbyqxmd.com/read/29757889/utilizing-t-cell-activation-signals-1-2-and-3-for-tumor-infiltrating-lymphocytes-til-expansion-the-advantage-over-the-sole-use-of-interleukin-2-in-cutaneous-and-uveal-melanoma
#11
René J Tavera, Marie-Andrée Forget, Young Uk Kim, Donastas Sakellariou-Thompson, Caitlin A Creasy, Ankit Bhatta, Orenthial J Fulbright, Renjith Ramachandran, Shawne T Thorsen, Esteban Flores, Arely Wahl, Audrey M Gonzalez, Christopher Toth, Seth Wardell, Rahmatu Mansaray, Laszlo G Radvanyi, Dan S Gombos, Sapna P Patel, Patrick Hwu, Rodabe N Amaria, Chantale Bernatchez, Cara Haymaker
In this study, we address one of the major critiques for tumor-infiltrating lymphocyte (TIL) therapy-the time needed for proper expansion of a suitable product. We postulated that T-cell receptor activation in the first phase of expansion combined with an agonistic stimulation of CD137/4-1BB and interleukin-2 would favor preferential expansion of CD8 TIL. Indeed, this novel 3-signal approach for optimal T-cell activation resulted in faster and more consistent expansion of CD8CD3 TIL. This new method allowed for successful expansion of TIL from cutaneous and uveal melanoma tumors in 100% of the cultures in <3 weeks...
May 11, 2018: Journal of Immunotherapy
https://www.readbyqxmd.com/read/29756253/prognostic-stratification-of-patients-with-nasopharyngeal-carcinoma-based-on-tumor-immune-microenvironment
#12
Takeharu Ono, Koichi Azuma, Akihiko Kawahara, Tetsuro Sasada, Norikazu Matsuo, Tatsuyuki Kakuma, Hiroyuki Kamimura, Ririko Maeda, Chikayuki Hattori, Kotaro On, Kei Nagata, Fumihiko Sato, Shun-Ich Chitose, Buichiro Shin, Takeichiro Aso, Jun Akiba, Hirohito Umeno
BACKGROUND: Little is known about immune-related prognostic factors in patients with nasopharyngeal carcinoma (NPC). METHODS: We retrospectively reviewed 66 patients with NPC. Epstein-Barr virus (EBV) status, programmed cell death-ligand 1 (PD-L1) expression, and tumor-infiltrating lymphocyte (TIL) densities were analyzed, and a prognostic evaluation of these immune-related parameters was performed. RESULTS: The multivariate analyses demonstrated that CD8-positive TIL density but not PD-L1 expression on tumor cells or immune cells was a significant predictive factor for progression-free survival (PFS) and overall survival (OS)...
May 13, 2018: Head & Neck
https://www.readbyqxmd.com/read/29755109/regulated-intratumoral-expression-of-il-12-using-a-rheoswitch-therapeutic-system-%C3%A2-rts-%C3%A2-gene-switch-as-gene-therapy-for-the-treatment-of-glioma
#13
John A Barrett, Hongliang Cai, John Miao, Pranay D Khare, Paul Gonzalez, Jessica Dalsing-Hernandez, Geeta Sharma, Tim Chan, Laurence J N Cooper, Francois Lebel
The purpose of this study was to determine if localized delivery of IL-12 encoded by a replication-incompetent adenoviral vector engineered to express IL-12 via a RheoSwitch Therapeutic System® (RTS® ) gene switch (Ad-RTS-IL-12) administered intratumorally which is inducibly controlled by the oral activator veledimex is an effective approach for glioma therapy. Mice bearing 5-10-day-old intracranial GL-261 gliomas were intratumorally administered Ad-RTS-mIL-12 in which IL-12 protein expression is tightly controlled by the activator ligand, veledimex...
May 14, 2018: Cancer Gene Therapy
https://www.readbyqxmd.com/read/29754847/feasibility-of-classification-of-triple-negative-breast-cancer-by-immunohistochemical-surrogate-markers
#14
Sewha Kim, Byung-In Moon, Woosung Lim, Sanghui Park, Min Sun Cho, Sun Hee Sung
INTRODUCTION: Recently, Burstein et al identified 4 stable molecular subtypes of triple negative breast cancer (TNBC) by mRNA profiling: luminal androgen receptor (LAR), mesenchymal (MES), basal-like immune-activated (BLIA), and basal-like immune-suppressive (BLIS) types. The purpose of this study was to assess the feasibility of immunohistochemistry (IHC) surrogate panel in classifying the TNBC molecular subtypes using a large cohort of TNBC retrieved from a single institution. MATERIALS AND METHODS: IHC for androgen receptor [AR], claudin-3, E-cadherin, cytokeratin 5/6 [CK5/6], epidermal growth factor receptor [EGFR], indoleamine 2,3-dioxygenase 1 [IDO1], and Forkhead box C1 [FOXC1] were performed using the tissue microarray constructed from 200 TNBC samples...
March 23, 2018: Clinical Breast Cancer
https://www.readbyqxmd.com/read/29754820/interfaces-of-malignant-and-immunologic-clonal-dynamics-in-ovarian-cancer
#15
Allen W Zhang, Andrew McPherson, Katy Milne, David R Kroeger, Phineas T Hamilton, Alex Miranda, Tyler Funnell, Nicole Little, Camila P E de Souza, Sonya Laan, Stacey LeDoux, Dawn R Cochrane, Jamie L P Lim, Winnie Yang, Andrew Roth, Maia A Smith, Julie Ho, Kane Tse, Thomas Zeng, Inna Shlafman, Michael R Mayo, Richard Moore, Henrik Failmezger, Andreas Heindl, Yi Kan Wang, Ali Bashashati, Diljot S Grewal, Scott D Brown, Daniel Lai, Adrian N C Wan, Cydney B Nielsen, Curtis Huebner, Basile Tessier-Cloutier, Michael S Anglesio, Alexandre Bouchard-Côté, Yinyin Yuan, Wyeth W Wasserman, C Blake Gilks, Anthony N Karnezis, Samuel Aparicio, Jessica N McAlpine, David G Huntsman, Robert A Holt, Brad H Nelson, Sohrab P Shah
High-grade serous ovarian cancer (HGSC) exhibits extensive malignant clonal diversity with widespread but non-random patterns of disease dissemination. We investigated whether local immune microenvironment factors shape tumor progression properties at the interface of tumor-infiltrating lymphocytes (TILs) and cancer cells. Through multi-region study of 212 samples from 38 patients with whole-genome sequencing, immunohistochemistry, histologic image analysis, gene expression profiling, and T and B cell receptor sequencing, we identified three immunologic subtypes across samples and extensive within-patient diversity...
May 7, 2018: Cell
https://www.readbyqxmd.com/read/29754071/aging-increases-susceptibility-to-ovarian-cancer-metastasis-in-murine-allograft-models-and-alters-immune-composition-of-peritoneal-adipose-tissue
#16
Elizabeth A Loughran, Annemarie K Leonard, Tyvette S Hilliard, Ryan C Phan, Madeleine G Yemc, Elizabeth Harper, Emma Sheedy, Yuliya Klymenko, Marwa Asem, Yueying Liu, Jing Yang, Jeff Johnson, Laura Tarwater, Zonggao Shi, Matthew Leevy, Matthew J Ravosa, M Sharon Stack
Ovarian cancer, the most deadly gynecological malignancy in U.S. women, metastasizes uniquely, spreading through the peritoneal cavity and often generating widespread metastatic sites before diagnosis. The vast majority of ovarian cancer cases occur in women over 40 and the median age at diagnosis is 63. Additionally, elderly women receive poorer prognoses when diagnosed with ovarian cancer. Despite age being a significant risk factor for the development of this cancer, there are little published data which address the impact of aging on ovarian cancer metastasis...
May 10, 2018: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/29750176/adoptive-cell-therapy-with-tumor-infiltrating-lymphocytes-in-advanced-melanoma-patients
#17
Mélanie Saint-Jean, Anne-Chantal Knol, Christelle Volteau, Gaëlle Quéreux, Lucie Peuvrel, Anabelle Brocard, Marie-Christine Pandolfino, Soraya Saiagh, Jean-Michel Nguyen, Christophe Bedane, Nicole Basset-Seguin, Amir Khammari, Brigitte Dréno
Immunotherapy for melanoma includes adoptive cell therapy with autologous tumor-infiltrating lymphocytes (TILs). This monocenter retrospective study was undertaken to evaluate the efficacy and safety of this treatment of patients with advanced melanoma. All advanced melanoma patients treated with TILs using the same TIL expansion methodology and same treatment interleukin-2 (IL-2) regimen between 2009 and 2012 were included. After sterile intralesional excision of a cutaneous or subcutaneous metastasis, TILs were produced according to a previously described method and then infused into the patient who also received a complementary subcutaneous IL-2 regimen...
2018: Journal of Immunology Research
https://www.readbyqxmd.com/read/29748589/prognostic-impact-of-tumor-infiltrating-lymphocytes-on-patients-with-metastatic-urothelial-carcinoma-receiving-platinum-based-chemotherapy
#18
Hui-Shan Huang, Harvey Yu-Li Su, Pei-Hsu Li, Po-Hui Chiang, Cheng-Hua Huang, Chien-Hsu Chen, Meng-Che Hsieh
The impact of tumor infiltrating lymphocytes (TILs) on survival was confirmed in various cancer types. Our study aims to investigate the prognostic role of TILs on survival in patients with metastatic urothelial carcinoma (mUC) receiving platinum based chemotherapy. Patients who were diagnosed to have pathologically proved mUC between 1997 and 2016 and received palliative chemotherapy with platinum based regimen were recruited into our study. Kaplan-Meier curves and Cox regression analysis were constructed for overall survival (OS)...
May 10, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29745829/a-gene-profiling-deconvolution-approach-to-estimating-immune-cell-composition-from-complex-tissues
#19
Shu-Hwa Chen, Wen-Yu Kuo, Sheng-Yao Su, Wei-Chun Chung, Jen-Ming Ho, Henry Horng-Shing Lu, Chung-Yen Lin
BACKGROUND: A new emerged cancer treatment utilizes intrinsic immune surveillance mechanism that is silenced by those malicious cells. Hence, studies of tumor infiltrating lymphocyte populations (TILs) are key to the success of advanced treatments. In addition to laboratory methods such as immunohistochemistry and flow cytometry, in silico gene expression deconvolution methods are available for analyses of relative proportions of immune cell types. RESULTS: Herein, we used microarray data from the public domain to profile gene expression pattern of twenty-two immune cell types...
May 8, 2018: BMC Bioinformatics
https://www.readbyqxmd.com/read/29743124/effects-of-habitat-fragmentation-on-the-genetic-diversity-and-differentiation-of-dendrolimus-punctatus-lepidoptera-lasiocampidae-in-thousand-island-lake-china-based-on-mitochondrial-coi-gene-sequences
#20
K Lv, J-R Wang, T-Q Li, J Zhou, J-Q Gu, G-X Zhou, Z-H Xu
Thousand Island Lake (TIL) is a typical fragmented landscape and an ideal model to study ecological effects of fragmentation. Partial fragments of the mitochondrial cytochrome oxidase subunit I gene of 23 island populations of Dendrolimus punctatus in TIL were sequenced, 141 haplotypes being identified. The number of haplotypes increased significantly with the increase in island area and shape index, whereas no significant correlation was detected between three island attributes (area, shape and isolation) and haplotype diversity...
May 10, 2018: Bulletin of Entomological Research
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