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https://www.readbyqxmd.com/read/29351920/exceptional-response-to-pembrolizumab-in-a-metastatic-chemotherapy-radiation-resistant-ovarian-cancer-patient-harboring-a-cd274-pd-l1-genetic-rearrangement
#1
Stefania Bellone, Natalia Buza, Jungmin Choi, Luca Zammataro, Laurie Gay, Julia A Elvin, David L Rimm, Yuting Liu, Elena Ratner, Peter E Schwartz, Alessandro D Santin
PURPOSE: Ovarian carcinoma no longer responsive to surgery and chemotherapy remains an incurable disease. Alternative therapeutic options remain desperately needed. EXPERIMENTAL DESIGN: We describe a heavily pretreated ovarian cancer patient with recurrent disease experiencing a remarkable clinical response to treatment with the anti-PD1 immune check-point inhibitor pembrolizumab. The clinical, pathological, and genomic characteristics of this exceptional ovarian cancer responder were carefully investigated using immunohistochemistry (IHC), quantitative multiplex fluorescence methods (ie, automated quantitative analysis, AQUA) and whole exome sequencing (WES) techniques...
January 19, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29344893/profiling-tumor-infiltrating-immune-cells-with-cibersort
#2
Binbin Chen, Michael S Khodadoust, Chih Long Liu, Aaron M Newman, Ash A Alizadeh
Tumor infiltrating leukocytes (TILs) are an integral component of the tumor microenvironment and have been found to correlate with prognosis and response to therapy. Methods to enumerate immune subsets such as immunohistochemistry or flow cytometry suffer from limitations in phenotypic markers and can be challenging to practically implement and standardize. An alternative approach is to acquire aggregative high dimensional data from cellular mixtures and to subsequently infer the cellular components computationally...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29340095/tumoral-immune-infiltrate-if-pd-l1-expression-and-role-of-cd8-tia-1-lymphocytes-in-localized-osteosarcoma-patients-treated-within-protocol-isg-os1
#3
Emanuela Palmerini, Claudio Agostinelli, Piero Picci, Stefano Pileri, Teresa Marafioti, Pier-Luigi Lollini, Katia Scotlandi, Alessandra Longhi, Maria Serena Benassi, Stefano Ferrari
Background: We hypothesized that immune-infiltrates were associated with superior survival, and examined a primary osteosarcoma tissue microarrays (TMAs) to test this hypothesis. Methods: 129 patients (pts) with localized osteosarcoma treated within protocol ISG-OS1 were included in the study. Clinical characteristics, expression of CD8, CD3, FOXP3, CD20, CD68/CD163 (tumor associated macrophage, TAM), Tia-1 (cytotoxic T cell), CD303 (plasmacytoid dendritic cells: pDC), Arginase-1 (myeloid derived suppressor cells: MDSC), PD-1 on immune-cells (IC), and PD-L1 on tumoral cells (TC) and IC were analysed and correlated with outcome...
December 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29338138/could-cryopreserved-human-semen-samples-be-stored-at-80%C3%A2-c
#4
Carlos R Vaz, Tamara Lamim, Rafael A Salvador, Anna P B Batschauer, Vera Lucia L Amaral, David Til
OBJECTIVE: To evaluate storage time effects in cryopreserved human semen samples, kept in the freezer at a controlled temperature of -80°C, on sperm viability after thawing. METHODS: We used 20 semen samples. Each sample was cryopreserved in 10 fingers, which were divided into five groups: one group was kept in cryogenic canisters throughout the experiment(control), and four groups were kept in a VIP Ultra Low MDF-U76V- PE freezer, with the temperature set at -80°C, for 24, 48, 72 and 96 hours, respectively...
January 17, 2018: JBRA Assisted Reproduction
https://www.readbyqxmd.com/read/29336717/pd1-protein-expression-in-tumor-infiltrated-lymphocytes-rather-than-pdl1-in-tumor-cells-predicts-survival-in-triple-negative-breast-cancer
#5
Xinyu Ren, Huanwen Wu, Junliang Lu, Yuhan Zhang, Yufeng Luo, Qianqian Xu, Songjie Shen, Zhiyong Liang
ABASTRACT To determine PD1/PDL1 expression status in triple-negative breast cancer (TNBC) at both protein and mRNA levels, and to analyze the relationship between their expression and clinical parameters of the TNBC patients. Immunohistochemistry and RNAscope were used to semi quantitively evaluate PD1/PDL1 protein and mRNA expression in 195 TNBC cases on tissue microarrays. Tumor infiltrating lymphocyte (TILs) abundance was assessed using hematoxylin-eosin staining.Both tumor cells and TILs expressed PDL1...
January 16, 2018: Cancer Biology & Therapy
https://www.readbyqxmd.com/read/29335154/local-administration-of-tiludronic-acid-downregulates-important-mediators-involved-in-periodontal-tissue-destruction-in-experimental-periodontitis-in-rats
#6
Flávia A C Furlaneto, Nara L T Nunes, Ricardo B Souza, Kely O Yamamoto, Ivan Lima Oliveira Filho, Nicolly P R Frota, Hellíada Chaves, Mario Lisboa, Mario Taba, Edilson Ervolino, Michel R Messora
OBJECTIVE: The purpose of this study was to evaluate whether local administration of TIL could influence the expression of the inflammatory mediators IL-1β, TNF-α, MMP-8 and COX-2 in rats with experimental periodontitis (EP). METHODS: Twenty-four adult male rats (Rattus norvegicus, albinus, Wistar) were assigned to groups C, EP, EP-TIL (CControl group, EP-Periodontitis groups). On EP groups, a ligature was placed around maxillary 2nd molars on day 1. On group EP-TIL, 20 μL of TIL solution (1 mg/kg body weight) was injected into the subperiosteal palatal area adjacent to the maxillary 2nd molar every other day until euthanasia (day 11)...
January 9, 2018: Archives of Oral Biology
https://www.readbyqxmd.com/read/29334492/anti-il-10-mediated-enhancement-of-antitumor-efficacy-of-a-dendritic-cell-targeting-mip3%C3%AE-gp100-vaccine-in-the-b16f10-mouse-melanoma-model-is-dependent-on-type-i-interferons
#7
James T Gordy, Kun Luo, Brian Francica, Charles Drake, Richard B Markham
The chemokine MIP3α (CCL20) binds to CCR6 on immature dendritic cells. Vaccines fusing MIP3α to gp100 have been shown to be effective in therapeutically reducing melanoma tumor burden and prolonging survival in a mouse model. Other studies have provided evidence that interleukin-10 (IL-10) neutralizing antibodies (αIL-10) enhance immunologic melanoma therapies by modulating the tolerogenic tumor microenvironment. In the current study, we have utilized the B16F10 syngeneic mouse melanoma model to demonstrate for the first time that a therapy neutralizing IL-10 enhances the antitumor efficacy of a MIP3α-gp100 DNA vaccine, leading to significantly smaller tumors, slower growing tumors, and overall increases in mouse survival...
January 12, 2018: Journal of Immunotherapy
https://www.readbyqxmd.com/read/29332341/association-of-the-combined-parameters-including-the-frequency-of-primary-cilia-cd8-tumor-infiltrating-lymphocytes-and-pd-1-expression-with-the-outcome-in-intestinal-cancer
#8
Josef Dvorak, Dimitar Hadzi Nikolov, Ladislav Dusek, Alzbeta Filipova, Igor Richter, David Buka, Ales Ryska, Jaroslav Mokry, Stanislav Filip, Bohuslav Melichar, Tomas Buchler, Jitka Abrahamova
PURPOSE: Primary cilium (PC) is considered to be a functional homologue of the immune synapse. Microtubule structures, PC of cancer associated fibroblasts and immune synapses between cytotoxic CD8+ tumor infiltrating lymphocytes (TILs) and cancer cells, are regularly found in varying amounts in the microenvironment of solid tumors. The purpose of this study was to find out the potential association and combined prognostic significance of the frequency of PC, PD-1 and CD8+ TILs in patients with intestinal cancer...
November 2017: Journal of B.U.ON.: Official Journal of the Balkan Union of Oncology
https://www.readbyqxmd.com/read/29330719/prognostic-value-of-tumor-infiltrating-lymphocyte-density-assessed-using-a-standardized-method-based-on-molecular-subtypes-and-adjuvant-chemotherapy-in-invasive-breast-cancer
#9
Nuri Jang, Hee Jung Kwon, Min Hui Park, Su Hwan Kang, Young Kyung Bae
BACKGROUND: This study investigated the prognostic value of tumor-infiltrating lymphocyte (TIL) density as determined by molecular subtype and receipt of adjuvant chemotherapy in invasive breast cancer (IBC). METHODS: Stromal TIL densities were evaluated in 1489 IBC samples using recommendations proposed by the International TILs Working Group. Cases were allocated to high- and low-TIL density groups using a cutoff of 10%. RESULTS: Of the 1489 IBC patients, 427 (28...
January 12, 2018: Annals of Surgical Oncology
https://www.readbyqxmd.com/read/29324844/absence-of-myeloid-klf4-reduces-prostate-cancer-growth-with-pro-atherosclerotic-activation-of-tumor-myeloid-cells-and-infiltration-of-cd8-t-cells
#10
David J Barakat, Rahul Suresh, Theresa Barberi, Kenneth J Pienta, Brian W Simons, Alan D Friedman
The microenvironment of prostate cancer often includes abundant tumor-associated macrophages (TAMs), with their acquisition of an M2 phenotype correlating with local aggressiveness and metastasis. Tumor-derived M-CSF contributes to TAM M2 polarization, and M-CSF receptor inhibition slows prostate cancer growth in model systems. As additional cytokines can direct TAM M2 polarization, targeting downstream transcription factors could avoid resistance. Klf4 and C/EBPβ each contribute to monocyte development, and reduced expression of macrophage Klf4 or C/EBPβ favors their adoption of a pro-inflammatory M1 state...
2018: PloS One
https://www.readbyqxmd.com/read/29324423/effects-of-omega-3-fatty-acids-against-chemotherapy-induced-mucositis-a-double-blind-randomized-clinical-trial
#11
Maryam Alsadat Hashemipour, Samaneh Barzegari, Shahla Kakoie, Raha Habib Aghahi
OBJECTIVE: This double-blind randomized clinical trial evaluates the ef cacy and route of administration of omega-3 fatty acids for the prevention and treatment of oral mucositis in patients undergoing che- motherapy in Iranian hospitals. MATERIALS AND METHODS: Sixty patients developing World Health Organization (WHO) grade 1 oral mucositis were randomized to the omega-3 fatty acid (n=30) or placebo (n=30) group. Mucositis was assessed according to the WHO, Western Consortium for Cancer Nursing Research, and Oral Mucositis Weekly Questionnaire cri- teria at baseline and rst, second, and third weeks of chemotherapy un- til mucositis resolved...
December 2017: Wounds: a Compendium of Clinical Research and Practice
https://www.readbyqxmd.com/read/29320521/cd8-t-cell-infiltration-in-breast-and-colon-cancer-a-histologic-and-statistical-analysis
#12
James Ziai, Houston N Gilbert, Oded Foreman, Jeffrey Eastham-Anderson, Felix Chu, Mahrukh Huseni, Jeong M Kim
The prevalence of cytotoxic tumor infiltrating lymphocytes (TILs) has demonstrated prognostic value in multiple tumor types. In particular, CD8 counts (in combination with CD3 and CD45RO) have been shown to be superior to traditional UICC staging in colon cancer patients and higher total CD8 counts have been associated with better survival in breast cancer patients. However, immune infiltrate heterogeneity can lead to potentially significant misrepresentations of marker prevalence in routine histologic sections...
2018: PloS One
https://www.readbyqxmd.com/read/29313457/the-predictive-value-and-role-of-stromal-tumor-infiltrating-lymphocytes-in-pancreatic-ductal-adenocarcinoma-pdac
#13
Tao Lianyuan, Xiu Dianrong, Yuan Chunhui, Ma Zhaolai, Jiang Bin
Recently, increasing evidence has indicated that the presence of tumor infiltrating immune cells has shown predictive significance for many solid tumors. Present study was performed to evaluate the predictive value of stromal tumor-infiltrating lymphocytes (TILs) for the presence of liver metastasis and overall survival in PDAC (pancreatic ductal adenocarcinoma) patients after complete resection and to explore the potential role of lymphocytes in PDAC. A total of 155 resectable patients with PDAC were enrolled in our study...
January 9, 2018: Cancer Biology & Therapy
https://www.readbyqxmd.com/read/29306022/t-regulatory-cells-mediate-immunosuppresion-by-adenosine-in-peripheral-blood-sentinel-lymph-node-and-tils-from-melanoma-patients
#14
P Di Gennaro, G Gerlini, R Caporale, S Sestini, P Brandani, C Urso, N Pimpinelli, L Borgognoni
T regulatory cells (Tregs), involved in tumour tolerance, can generate Adenosine by CD39/CD73 surface enzymes, which identify four Tregs subsets: CD39+CD73- nTregs, CD39+CD73+ iTregs, CD39-CD73+ oTregs and CD39-CD73- xTregs. In melanoma patients, increased Tregs levels are detected in peripheral blood (PB), sentinel lymph node (SLN) and tumour infiltrating lymphocytes (TILs), but Adenosine role was not investigated yet. We examined total Tregs and Adenosine subsets in PB, SLN and TILs from melanoma patients (n = 32) and PB from healthy donors (HD; n = 10) by flow cytometry...
January 3, 2018: Cancer Letters
https://www.readbyqxmd.com/read/29302378/potential-utility-of-fdg-pet-ct-as-a-non-invasive-tool-for-monitoring-local-immune-responses
#15
Seungho Lee, Seohee Choi, Sang Yong Kim, Mi Jin Yun, Hyoung-Il Kim
Purpose: The tumor microenvironment is known to be associated with the metabolic activity of cancer cells and local immune reactions. We hypothesized that glucose metabolism measured by 2-deoxy-2-(18F)fluoro-D-glucose (18F-FDG) positron emission tomography (PET)-computed tomography (CT) (18F-FDG PET-CT) would be associated with local immune responses evaluated according to the presence of tumor infiltrating lymphocytes (TILs). Materials and Methods: We retrospectively reviewed 56 patients who underwent 18F-FDG PET-CT prior to gastrectomy...
December 2017: Journal of Gastric Cancer
https://www.readbyqxmd.com/read/29301752/t-cell-responses-in-the-microenvironment-of-primary-renal-cell-carcinoma-implications-for-adoptive-cell-therapy
#16
Rikke Andersen, Marie Christine Wulff Westergaard, Julie Westerlin Kjeldsen, Anja Mueller, Natasja Wulff Pedersen, Sine Reker Hadrup, Ozcan Met, Barbara Seliger, Bjarne Kromann-Andersen, Thomas Hasselager, Marco Donia, Inge Marie Svane
In vitro expansion of large numbers of highly potent tumor-reactive T cells appears a prerequisite for effective adoptive cell therapy (ACT) with autologous tumor-infiltrating lymphocytes (TIL) as shown in metastatic melanoma (MM). We therefore sought to determine whether renal cell carcinomas (RCC) are infiltrated with tumor-reactive T cells that could be efficiently employed for adoptive transfer immunotherapy. TILs and autologous tumor cell lines (TCLs) were successfully generated from 22 (92%) and 17 (77%) of 24 consecutive primary RCC specimens and compared to those generated from MM...
January 4, 2018: Cancer Immunology Research
https://www.readbyqxmd.com/read/29301097/phase-amplitude-coupling-a-general-mechanism-for-memory-processing-and-synaptic-plasticity
#17
Til O Bergmann, Jan Born
In this issue of Neuron, Helfrich et al. (2017) demonstrate that phase-amplitude coupling (PAC) between slow oscillations and spindles is crucial for memory consolidation, and shifts in its phase relationship may explain age-related deficits in memory performance. These results also suggest a more general function of PAC in synaptic plasticity.
January 3, 2018: Neuron
https://www.readbyqxmd.com/read/29296194/changes-in-pd-l1-expression-according-to-tumor-infiltrating-lymphocytes-of-acquired-egfr-tki-resistant-egfr-mutant-non-small-cell-lung-cancer
#18
Tae-Jung Kim, Soon Auck Hong, Okran Kim, Seung Joon Kim, Ji-Hyun Yang, Eun Kyo Joung, Jin-Hyoung Kang, Sook-Hee Hong
Backgrounds: EGFR-mutant non-small cell lung cancer (NSCLC) that developed acquired resistance to EGFR-tyrosine kinase (TKI) are potential candidates for programmed death 1 (PD1) inhibitor. Results: TPS≥1% for PD-L1 and low CD8 + TIL in post-TKI tumor showed a trend for a lower PFS of EGFR-TKIs (14.2 vs 9.9 months; P = 0.060) (cohort A). Only 2 of 22 specimens (9.1%) with an acquired EGFR exon 20 T790M mutation exhibited in post-TKI TPS≥50% for PD-L1. The degree in post-TKI tumor of PD-L1 expression was varied in 19 patients (40...
December 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/29290777/classifying-non-small-cell-lung-cancer-by-status-of-programmed-cell-death-ligand-1-and-tumor-infiltrating-lymphocytes-on-tumor-cells
#19
Shaohua Cui, Lili Dong, Jialin Qian, Lin Ye, Liyan Jiang
Purpose: To explore the possible correlation between programmed death ligand 1 (PD-L1)/tumor-infiltrating lymphocytes (TIL) status and clinical factors in non-small cell lung (NSCLC). Materials and Methods: A total of 126 surgical NSCLC samples with stage I to IIIA were retrospectively collected and analyzed. Immunohistochemistry (IHC) assays were used to detect PD-L1 protein expression. PD-L1 positivity on tumor cells was defined by positive tumor cell (TC) percentage using 5% cutoff value. Results: Thirty-seven patients (29...
2018: Journal of Cancer
https://www.readbyqxmd.com/read/29288043/tumor-associated-macrophages-and-the-tumor-immune-microenvironment-of-primary-and-recurrent-epithelial-ovarian-cancer-eoc
#20
Laureen S Ojalvo, Elizabeth D Thompson, Tian-Li Wang, Alan K Meeker, Ie-Ming Shih, Amanda N Fader, Ashley M Cimino-Mathews, Leisha A Emens
Tumor infiltrating lymphocytes (TILs) are associated with better prognosis in newly diagnosed epithelial ovarian cancer (EOC), but clinical trials of immunotherapies in patients with heavily-treated disease reveal limited activity. Understanding the tumor microenvironment (TME) of primary and recurrent EOC should guide future trials. Here, we evaluated the TME of paired primary and recurrent tumors (n=17), and non-paired primary (n=20) and recurrent (n=15) tumors, for CD8+ T cells, FOXP3+ regulatory T cells (Tregs), CD68+ tumor-associated macrophages (TAMs), programmed cell death protein 1 (PD-1) and programmed cell death ligand 1 (PD-L1)...
December 26, 2017: Human Pathology
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