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https://www.readbyqxmd.com/read/28107186/the-combination-of-pd-l1-expression-and-decreased-tumor-infiltrating-lymphocytes-is-associated-with-a-poor-prognosis-in-triple-negative-breast-cancer
#1
Hitomi Mori, Makoto Kubo, Rin Yamaguchi, Reiki Nishimura, Tomofumi Osako, Nobuyuki Arima, Yasuhiro Okumura, Masayuki Okido, Mai Yamada, Masaya Kai, Junji Kishimoto, Yoshinao Oda, Masafumi Nakamura
This study included patients with primary triple-negative breast cancer (TNBC) who underwent resection without neoadjuvant chemotherapy between January 2004 and December 2014. Among the 248 TNBCs studied, programmed cell death ligand-1 (PD-L1) expression was detected in 103 (41.5%) tumors, and high levels of tumor-infiltrating lymphocytes (TILs) were present in 118 (47.6%) tumors. PD-L1 expression correlated with high levels of TILs, but was not a prognostic factor. Patients with TILs-high tumors had better overall survival than those with TILs-low tumors (P = 0...
January 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/28105369/potassium-channels-of-t-lymphocytes-take-center-stage-in-the-fight-against-cancer
#2
EDITORIAL
Laura Conforti
A recent study by Eil at al. published in Nature in September 2016 provides evidence that alterations of the K(+) homeostasis of tumor infiltrating lymphocytes (TILs) in necrotic areas of the tumor microenvironment (TME) suppress the function of effector T cells. Furthermore, they establish that overexpression of K(+) channels in T lymphocytes counterbalances this negative effect of the TME and restores the ability of TILs to function, ultimately leading to increased survival of tumor bearing mice. Thus, K(+) channels in T lymphocytes become interesting new targets for novel immunotherapies in cancer...
2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28105157/prognostic-impact-of-the-tumor-infiltrating-regulatory-t-cell-foxp3-activated-cytotoxic-t-lymphocyte-granzyme-b-ratio-on-resected-left-sided-pancreatic-cancer
#3
Ho Kyoung Hwang, Hyoung-Il Kim, Se Hoon Kim, Junjeong Choi, Chang Moo Kang, Kyung Sik Kim, Woo Jung Lee
Among the subsets of tumor-infiltrating lymphocytes (TILs), activated cytotoxic T lymphocytes (granzyme B(+)) have an antitumor effect, while regulatory T lymphocytes [forkhead box P3 (Foxp3)(+)] suppress the antitumor immune response. The aim of the present study was to investigate the possible associations between TIL subsets and survival outcomes in patients with left-sided pancreatic ductal adenocarcinoma (PDAC). From January 2000 to December 2008, 30 patients who underwent curative distal pancreatectomy without neoadjuvant chemoradiotherapy due to left-sided PDAC were enrolled in the present study...
December 2016: Oncology Letters
https://www.readbyqxmd.com/read/28099920/prognostic-implications-of-intratumoral-cd103-tumor-infiltrating-lymphocytes-in-pulmonary-squamous-cell-carcinoma
#4
Jaemoon Koh, Sehui Kim, Moon-Young Kim, Heounjeong Go, Yoon Kyung Jeon, Doo Hyun Chung
CD103 is the αE subunit of αEβ7 integrin that is expressed in tissue-resident memory T cells, where it promotes cytotoxic T cell responses against tumors. However, little is known about its expression or clinicopathological implications in non-small cell lung cancer (NSCLC). This study investigated the prognostic implications of CD103+ tumor-infiltrating lymphocytes (TILs) in NSCLC. We established two cohorts: patients with resected NSCLC (n = 132) and patients with pulmonary squamous cell carcinoma (pSCC), a subset of NSCLC (n = 378), to estimate the prognostic significance of CD103+ TILs...
January 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/28093487/a-pilot-trial-of-the-combination-of-vemurafenib-with-adoptive-cell-therapy-in-patients-with-metastatic-melanoma
#5
Drew C Deniger, Mei Li M Kwong, Anna Pasetto, Mark E Dudley, John R Wunderlich, Michelle M Langhan, Chyi-Chia Richard Lee, Steven A Rosenberg
PURPOSE: This pilot feasibility clinical trial evaluated the coadministration of vemurafenib, a small-molecule antagonist of BRAF(V600) mutations, and tumor-infiltrating lymphocytes (TIL) for the treatment of metastatic melanoma. EXPERIMENTAL DESIGN: A metastatic tumor was resected for growth of TILs, and patients were treated with vemurafenib for 2 weeks, followed by resection of a second lesion. Patients then received a nonmyeloablative preconditioning regimen, infusion of autologous TILs, and high-dose interleukin-2 administration...
January 15, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28093446/tumor-infiltrating-merkel-cell-polyomavirus-specific-t-cells-are-diverse-and-associated-with-improved-patient-survival
#6
Natalie J Miller, Candice D Church, Lichun Dong, David Crispin, Matthew P Fitzgibbon, Kristina Lachance, Lichen Jing, Michi Shinohara, Ioannis Gavvovidis, Gerald Willimsky, Martin McIntosh, Thomas Blankenstein, David M Koelle, Paul Nghiem
Tumor-infiltrating CD8(+) T cells are associated with improved survival of patients with Merkel cell carcinoma (MCC), an aggressive skin cancer causally linked to Merkel cell polyomavirus (MCPyV). However, CD8(+) T-cell infiltration is robust in only 4% to 18% of MCC tumors. We characterized the T-cell receptor (TCR) repertoire restricted to one prominent epitope of MCPyV (KLLEIAPNC, "KLL") and assessed whether TCR diversity, tumor infiltration, or T-cell avidity correlated with clinical outcome. HLA-A*02:01/KLL tetramer(+) CD8(+) T cells from MCC patient peripheral blood mononuclear cells (PBMC) and tumor-infiltrating lymphocytes (TIL) were isolated via flow cytometry...
January 16, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28070966/the-1-min-screening-test-for-reading-problems-in-college-students-psychometric-properties-of-the-1-min-til
#7
Tânia Fernandes, Susana Araújo, Ana Sucena, Alexandra Reis, São Luís Castro
Reading is a central cognitive domain, but little research has been devoted to standardized tests for adults. We, thus, examined the psychometric properties of the 1-min version of Teste de Idade de Leitura (Reading Age Test; 1-min TIL), the Portuguese version of Lobrot L3 test, in three experiments with college students: typical readers in Experiment 1A and B, dyslexic readers and chronological age controls in Experiment 2. In Experiment 1A, test-retest reliability and convergent validity were evaluated in 185 students...
January 9, 2017: Dyslexia: the Journal of the British Dyslexia Association
https://www.readbyqxmd.com/read/28068603/rational-design-synthesis-and-evaluation-of-novel-2-4-chloro-and-hydroxy-substituted-diphenyl-benzofuro-3-2-b-pyridines-non-intercalative-catalytic-topoisomerase-i-and-ii-dual-inhibitor
#8
Seojeong Park, Til Bahadur Thapa Magar, Tara Man Kadayat, Hwa Jong Lee, Ganesh Bist, Aarajana Shrestha, Eung-Seok Lee, Youngjoo Kwon
Novel series of conformationally constrained 2,4-chloro- and hydroxy-substituted diphenyl benzofuro[3,2-b]pyridines were rationally designed and synthesized. Their biological activities were evaluated for topoisomerase I and II inhibitory activity, and antiproliferative activity against several human cancer cell lines for the development of novel anticancer agents. Most of the compounds with phenol moiety at 4-position of central pyridine exhibited significant dual topoisomerase I and II inhibitory activities, and strong antiproliferative activity in low micromolar range...
January 2, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28058578/pd-l1-expression-and-tumor-infiltrating-pd-1-%C3%A2-lymphocytes-associated-with-outcome-in-her2-%C3%A2-breast-cancer-patients
#9
Julia Y S Tsang, Wai-Ling Au, Kwan-Yin Lo, Yun-Bi Ni, Thazin Hlaing, Jintao Hu, Siu-Ki Chan, Kui-Fat Chan, Sai-Yin Cheung, Gary M Tse
PURPOSE: Clinical trials showing programmed death (PD)-1-PD-ligand 1 (L1) axis as a promising therapeutic target in melanoma and non-small cell lung cancers have made the pathway a focus of recent attention. However, the data regarding PD-L1/PD-1 in breast cancer are inconsistent. Given the heterogeneity of breast cancers, the clinical relevance of PD-L1 and PD-1 tumor infiltrating lymphocytes (TIL) may vary according to subtypes of breast cancer. We aim to investigate PD-L1 expression in a large cohort of breast cancers and analyze its clinico-pathological as well as outcome relationship according to molecular subtypes...
January 5, 2017: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/28050956/the-effects-of-storing-and-transporting-cryopreserved-semen-samples-on-dry-ice
#10
David Til, Vera L L Amaral, Rafael A Salvador, Alfred Senn, Thais S de Paula
OBJECTIVE: This study aimed to test the effects on sperm viability of transporting cryopreserved semen samples on dry ice. METHODS: Twenty normozoospermic semen samples were cryopreserved and divided into five groups. The samples in Group 1 were immersed in liquid nitrogen throughout the experiment in cryogenic storage tanks; the cryopreserved straws in Group 2 were placed in a Styrofoam box containing dry ice and kept under these conditions for 48 hours; the samples in Group 3 were kept for 48 hours on dry ice under the same conditions as the Group 2 samples, and were then moved to a storage tank filled with liquid nitrogen; Group 4 samples were also kept for 48 hours in dry ice storage, and the Styrofoam box containing the samples was shipped by plane to assess the effects of shipping; the samples in Group 5 were shipped together with the Group 4 samples and were placed in a storage tank with liquid nitrogen after spending 48 hours stored on dry ice...
December 1, 2016: JBRA Assisted Reproduction
https://www.readbyqxmd.com/read/28049579/tumour-infiltrating-lymphocytes-and-the-emerging-role-of-immunotherapy-in-breast-cancer
#11
Stephen J Luen, Peter Savas, Stephen B Fox, Roberto Salgado, Sherene Loi
Breast cancer has not previously been considered a highly immunogenic cancer. Observations of tumour-infiltrating lymphocytes (TILs) in and around neoplastic cells in tumour samples, and associations with improved pathological complete response and clinical survival end points have changed our perspective on this. Lymphocytic infiltrates have long been observed in breast cancer; however, more recently, retrospective analysis of prospectively collected tissue samples from clinical trials has demonstrated the potential role of host immunosurveillance in influencing the biology of breast cancer...
December 31, 2016: Pathology
https://www.readbyqxmd.com/read/28041681/versatility-of-buccinator-flaps-for-the-treatment-of-palatal-defects-a-series-of-cases
#12
REVIEW
M A Gavin Clavero, M V Simón Sanz, Ú M Jariod Ferrer, A Mur Til
The buccinator flap is currently one of the best techniques for the reconstruction of defects in the oral cavity and other sites. Reconstruction of the palate is a major challenge because of the functional consequences of the excision of lesions in this area. The main goal is to maintain separation between the mouth and the nose. We have done a cross-sectional retrospective descriptive study of a series of cases reconstruction of palatal defects with buccinator flap at the University Hospital Miguel Servet in Zaragoza during a six-year period and compared our results, morbidity, and mortality with those of published series...
December 29, 2016: British Journal of Oral & Maxillofacial Surgery
https://www.readbyqxmd.com/read/28039329/a-genome-wide-interaction-analysis-of-tricyclic-tetracyclic-antidepressants-and-rr-and-qt-intervals-a-pharmacogenomics-study-from-the-cohorts-for-heart-and-aging-research-in-genomic-epidemiology-charge-consortium
#13
Raymond Noordam, Colleen M Sitlani, Christy L Avery, James D Stewart, Stephanie M Gogarten, Kerri L Wiggins, Stella Trompet, Helen R Warren, Fangui Sun, Daniel S Evans, Xiaohui Li, Jin Li, Albert V Smith, Joshua C Bis, Jennifer A Brody, Evan L Busch, Mark J Caulfield, Yii-Der I Chen, Steven R Cummings, L Adrienne Cupples, Qing Duan, Oscar H Franco, Rául Méndez-Giráldez, Tamara B Harris, Susan R Heckbert, Diana van Heemst, Albert Hofman, James S Floyd, Jan A Kors, Lenore J Launer, Yun Li, Ruifang Li-Gao, Leslie A Lange, Henry J Lin, Renée de Mutsert, Melanie D Napier, Christopher Newton-Cheh, Neil Poulter, Alexander P Reiner, Kenneth M Rice, Jeffrey Roach, Carlos J Rodriguez, Frits R Rosendaal, Naveed Sattar, Peter Sever, Amanda A Seyerle, P Eline Slagboom, Elsayed Z Soliman, Nona Sotoodehnia, David J Stott, Til Stürmer, Kent D Taylor, Timothy A Thornton, André G Uitterlinden, Kirk C Wilhelmsen, James G Wilson, Vilmundur Gudnason, J Wouter Jukema, Cathy C Laurie, Yongmei Liu, Dennis O Mook-Kanamori, Patricia B Munroe, Jerome I Rotter, Ramachandran S Vasan, Bruce M Psaty, Bruno H Stricker, Eric A Whitsel
BACKGROUND: Increased heart rate and a prolonged QT interval are important risk factors for cardiovascular morbidity and mortality, and can be influenced by the use of various medications, including tricyclic/tetracyclic antidepressants (TCAs). We aim to identify genetic loci that modify the association between TCA use and RR and QT intervals. METHODS AND RESULTS: We conducted race/ethnic-specific genome-wide interaction analyses (with HapMap phase II imputed reference panel imputation) of TCAs and resting RR and QT intervals in cohorts of European (n=45 706; n=1417 TCA users), African (n=10 235; n=296 TCA users) and Hispanic/Latino (n=13 808; n=147 TCA users) ancestry, adjusted for clinical covariates...
December 30, 2016: Journal of Medical Genetics
https://www.readbyqxmd.com/read/28038383/co-expression-of-tim-3-and-ceacam1-promotes-t-cell-exhaustion-in-colorectal-cancer-patients
#14
Yang Zhang, Pengcheng Cai, Lei Li, Liang Shi, Panpan Chang, Tao Liang, Qianqian Yang, Yang Liu, Lin Wang, Lihua Hu
T-cell immunoglobulin domain and mucin domain-3(TIM-3) is an activation induced inhibitory molecule involved in immune tolerance and is recently reported to induce T cell exhaustion which is mediated by carcinoembryonic antigen cell adhesion molecule 1(CEACAM1), another well-known molecule expressed on activated T cells and involved in T cell inhibition. To investigate the expression of TIM-3 and CEACAM1 on circulating CD8(+) T cells and tumor infiltrating lymphocytes (TILs), 65 diagnosed colorectal cancer (CRC) patients and 38 healthy controls were enrolled in this study and the results showed that TIM-3 and CEACAM1 were both highly expressed on circulating CD8(+) T cells in CRC patients and elevated on TILs compared with paraneoplastic T cells...
February 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28036275/lymphocyte-to-monocyte-ratio-is-associated-with-prognosis-of-diffuse-large-b-cell-lymphoma-correlation-with-cd163-positive-m2-type-tumor-associated-macrophages-not-pd-1-positive-tumor-infiltrating-lymphocytes
#15
Jingxuan Wang, Kun Gao, Wanting Lei, Lina Dong, Qijia Xuan, Meiyan Feng, Jinlu Wang, Xiangnan Ye, Tuan Jin, Zhongbai Zhang, Qingyuan Zhang
The research aims to examine the prognostic value of the lymphocyte-to-monocyte ratio (LMR), neutrophil-to- lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) in diffuse large B-cell lymphoma (DLBCL). The relation of these hematologic indicators to poor antitumor immunity and prognosis must be investigated. Clinicopathologic data and survival information of 355 patients with DLBCL was retrospectively analyzed. Univariate analysis revealed that lower LMR (<2.71), higher NLR (≥2.81), CD163+ M2 tumor-associated macrophages (TAM) content ≥9...
December 27, 2016: Oncotarget
https://www.readbyqxmd.com/read/28032290/tils-in-head-and-neck-cancer-ready-for-clinical-implementation-and-why-not
#16
REVIEW
Astrid De Meulenaere, Tijl Vermassen, Sandrine Aspeslagh, Katrien Vandecasteele, Sylvie Rottey, Liesbeth Ferdinande
The assessment of tumor infiltrating lymphocytes (TILs) has recently emerged as a prognostic biomarker in several solid tumors. Quantification and subtyping of TILs reflects the immune response in the tumor microenvironment, contributing to either tumoral immune attack or escape and thereby affecting outcome. Despite the growing evidence of its value as prognosticator, TILs analysis has not yet found its way to daily clinical practice. The aim of this review is to evaluate whether the current knowledge on TILs in head and neck cancer justifies its clinical implementation...
December 28, 2016: Head and Neck Pathology
https://www.readbyqxmd.com/read/28029650/tumor-infiltrating-lymphocytes-predict-prognosis-of-breast-cancer-patients-treated-with-anti-her-2-therapy
#17
Tan-Huan Chen, Ying-Chun Zhang, Yu-Ting Tan, Xin An, Cong Xue, Ying-Fei Deng, Wei Yang, Xia Yuan, Yan-Xia Shi
PURPOSE: Infiltration of tumor associated lymphocytes and count of its different phenotypes are potentially new independent predictor of prognosis in breast cancer. However, research related to it is less reported in breast cancer patients treated with anti-Her-2 therapy. Thus, we evaluated the relationship between survival and tumor infiltrating lymphocytes including its different phenotypes in tumors of such patients. METHODS: Between 1999 and 2010, 98 patients diagnosed with primary breast cancer and treated with anti-Her-2 therapy at Sun-Yat-Sen University Cancer Center were included in the study...
December 23, 2016: Oncotarget
https://www.readbyqxmd.com/read/28018970/interlesional-diversity-of-t-cell-receptors-in-melanoma-with-immune-checkpoints-enriched-in-tissue-resident-memory-t-cells
#18
Chandra Sekhar Boddupalli, Noffar Bar, Krishna Kadaveru, Michael Krauthammer, Natopol Pornputtapong, Zifeng Mai, Stephan Ariyan, Deepak Narayan, Harriet Kluger, Yanhong Deng, Rakesh Verma, Rituparna Das, Antonella Bacchiocchi, Ruth Halaban, Mario Sznol, Madhav V Dhodapkar, Kavita M Dhodapkar
Heterogeneity of tumor cells and their microenvironment can affect outcome in cancer. Blockade of immune checkpoints (ICPs) expressed only on a subset of immune cells leads to durable responses in advanced melanoma. Tissue-resident memory T (TRM) cells have recently emerged as a distinct subset of memory T cells in nonlymphoid tissues. Here, we show that functional properties and expression of ICPs within tumor-infiltrating lymphocytes (TILs) differ from those of blood T cells. TILs secrete less IL-2, IFN-γ, and TNF-α compared with circulating counterparts, and expression of VEGF correlated with reduced TIL infiltration...
December 22, 2016: JCI Insight
https://www.readbyqxmd.com/read/28018602/fusion-of-the-dendritic-cell-targeting-chemokine-mip3%C3%AE-to-melanoma-antigen-gp100-in-a-therapeutic-dna-vaccine-significantly-enhances-immunogenicity-and-survival-in-a-mouse-melanoma-model
#19
James T Gordy, Kun Luo, Hong Zhang, Arya Biragyn, Richard B Markham
BACKGROUND: Although therapeutic cancer vaccines have been mostly disappointing in the clinic, the advent of novel immunotherapies and the future promise of neoantigen-based therapies have created the need for new vaccine modalities that can easily adapt to current and future developments in cancer immunotherapy. One such novel platform is a DNA vaccine fusing the chemokine Macrophage Inflammatory Protein-3α (MIP-3α) to an antigen, here melanoma antigen gp100. Previous published work has indicated that MIP-3α targets nascent peptides to immature dendritic cells, leading to processing by class I and II MHC pathways...
2016: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28018343/very-late-antigen-1-marks-functional-tumor-resident-cd8-t-cells-and-correlates-with-survival-of-melanoma-patients
#20
Timothy Murray, Silvia A Fuertes Marraco, Petra Baumgaertner, Natacha Bordry, Laurène Cagnon, Alena Donda, Pedro Romero, Grégory Verdeil, Daniel E Speiser
A major limiting factor in the success of immunotherapy is tumor infiltration by CD8(+) T cells, a process that remains poorly understood. In the present study, we characterized homing receptors expressed by human melanoma-specific CD8(+) T cells. Our data reveal that P-selectin binding and expression of the retention integrin, very late antigen (VLA)-1, by vaccine-induced T cells correlate with longer patient survival. Furthermore, we demonstrate that CD8(+)VLA-1(+) tumor-infiltrating lymphocytes (TILs) are highly enriched in melanoma metastases in diverse tissues...
2016: Frontiers in Immunology
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