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https://www.readbyqxmd.com/read/28813410/identification-of-cmtm6-and-cmtm4-as-pd-l1-protein-regulators
#1
Riccardo Mezzadra, Chong Sun, Lucas T Jae, Raquel Gomez-Eerland, Evert de Vries, Wei Wu, Meike E W Logtenberg, Maarten Slagter, Elisa A Rozeman, Ingrid Hofland, Annegien Broeks, Hugo M Horlings, Lodewyk F A Wessels, Christian U Blank, Yanling Xiao, Albert J R Heck, Jannie Borst, Thijn R Brummelkamp, Ton N M Schumacher
The clinical benefit for patients with diverse types of metastatic cancers that has been observed upon blockade of the interaction between PD-1 and PD-L1 has highlighted the importance of this inhibitory axis in the suppression of tumour-specific T-cell responses. Notwithstanding the key role of PD-L1 expression by cells within the tumour micro-environment, our understanding of the regulation of the PD-L1 protein is limited. Here we identify, using a haploid genetic screen, CMTM6, a type-3 transmembrane protein of previously unknown function, as a regulator of the PD-L1 protein...
August 16, 2017: Nature
https://www.readbyqxmd.com/read/28811252/expression-of-alcam-cd166-and-pd-l1-cd274-independently-predicts-shorter-survival-in-malignant-pleural-mesothelioma
#2
Shingo Inaguma, Jerzy Lasota, Zengfeng Wang, Piotr Czapiewski, Renata Langfort, Janusz Rys, Joanna Szpor, Piotr Waloszczyk, Krzysztof Okoń, Wojciech Biernat, Hiroshi Ikeda, David S Schrump, Raffit Hassan, Markku Miettinen
Diffuse malignant mesothelioma of the pleura is a highly aggressive tumor typically associated with short survival. ALCAM (CD166), a type I transmembrane protein, is a member of the immunoglobulin superfamily. In normal cells, ALCAM regulates physiological processes such as angiogenesis and immune response. In cancer, it is associated with neoplastic progression, including invasion, migration, and metastasis. Furthermore, ALCAM is considered one of the cancer stem cell markers such as ALDH1 (ALDH1A1) and SALL4...
August 12, 2017: Human Pathology
https://www.readbyqxmd.com/read/28795418/cd274-pdl1-and-jak2-genomic-amplifications-in-pulmonary-squamous-cell-and-adenocarcinoma-patients
#3
Sergi Clavé, Lara Pijuan, David Casadevall, Álvaro Taus, Javier Gimeno, Sílvia Hernández-Llodrà, María Rodríguez-Rivera, Marta Lorenzo, Sílvia Menéndez, Joan Albanell, Blanca Espinet, Edurne Arriola, Marta Salido
AIMS: CD274 (PDL1) and JAK2 (9p24.1) gene amplifications have been recently described in pulmonary carcinomas in association with PD-L1 protein expression. Also, PTEN loss have been explored preclinically in relation with PD-L1 expression. It remains to be determined if these genomic alterations may affect PD-L1 expression levels in non-small cell lung cancer. METHODS AND RESULTS: PD-L1 and PTEN protein expression by IHC, and CD274, JAK2 and PTEN gene copy number alterations (CNAs) by FISH were studied in 171 pulmonary carcinoma specimens...
August 10, 2017: Histopathology
https://www.readbyqxmd.com/read/28762952/prediction-of-radio-responsiveness-with-immune-profiling-in-patients-with-rectal-cancer
#4
In Ja Park, Soyeon An, Sang-Yeob Kim, Hye Min Lim, Seung-Mo Hong, Mi-Ju Kim, Yun Jae Kim, Chang Sik Yu
We evaluate whether the tumor immune infiltrate (TIL) could be used for prediction of responsiveness to preoperative chemoradiotherapy (PCRT) in rectal cancers. Using formalin-fixed paraffin-embedded slides of pretreatment biopsies, co-stain for CD4, CD8, CD274 (PD-L1), FOXP3, cytokeratin, and DAPI was performed with Opal multi staining kit (Perkin-Elmer, Waltham, MA). Multispectral imaging and digital analysis to visualize and quantify specific immune infiltrates were performed using the Vectra imaging system (Perkin-Elmer)...
July 25, 2017: Oncotarget
https://www.readbyqxmd.com/read/28713995/bioinformatic-analysis-of-computational-identified-differentially-expressed-genes-in-tumor-stoma-of-pregnancy%C3%A2-associated-breast-cancer
#5
Qian Zhou, Erhu Sun, Lijun Ling, Xiaofeng Liu, Min Zhang, Hong Yin, Cheng Lu
The present study aimed to screen the differentially expressed genes (DEGs) in tumor‑associated stroma of pregnancy‑associated breast cancer (PABC). By analyzing Affymetrix microarray data (GSE31192) from the Gene Expression Omnibus database, DEGs between tumor asso-ciated stromal cells and normal stromal cells in PABC were identified. Gene Ontology (GO) function and pathway enrichment analyses for the DEGs were then performed, followed by construction of a protein‑protein interaction (PPI) network. A total of 94 upregulated and 386 downregulated DEGs were identified between tumor associated stromal cells and normal stromal cells in patients with PABC...
September 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28667193/pd-l1-protein-expression-in-tumour-cells-and-immune-cells-in-mismatch-repair-protein-deficient-and-proficient-colorectal-cancer-the-foundation-study-using-the-sp142-antibody-and-whole-section-immunohistochemistry
#6
Tony El Jabbour, Jeffrey S Ross, Christine E Sheehan, Kajsa E Affolter, Katherine B Geiersbach, Ann Boguniewicz, Sanaz Ainechi, Mary P Bronner, David M Jones, Hwajeong Lee
AIMS: Routine application of PD-L1 immunohistochemistry (IHC) in colorectal cancer (CRC) is limited due to lack of standardized scoring criteria, antibody clones, and intratumoral staining heterogeneity. We assessed PD-L1 protein expression on full face CRC tissue sections and applied two algorithms based on the published clinical trials that support the recent FDA approval for immune checkpoint inhibitors (ICPI) therapy in non-small cell lung cancer (NSCLC). METHODS: PD-L1/CD274 IHC (Roche/Ventana, clone SP142) was performed on representative tumour blocks from 52 mismatch repair-deficient (MMR-D) and 52 MMR-proficient (MMR-P) CRCs...
June 30, 2017: Journal of Clinical Pathology
https://www.readbyqxmd.com/read/28652380/immune-escape-in-breast-cancer-during-in-situ-to-invasive-carcinoma-transition
#7
Carlos R Gil Del Alcazar, Sung Jin Huh, Muhammad B Ekram, Anne Trinh, Lin L Liu, Francisco Beca, Xiaoyuan Zi, Minsuk Kwak, Helga Bergholtz, Ying Su, Lina Ding, Hege G Russnes, Andrea L Richardson, Kirsten Babski, Elizabeth Min Hui Kim, Charles McDonnell, Jon Wagner, Ron Rowberry, Gordon J Freeman, Deborah Dillon, Therese Sorlie, Lisa M Coussens, Judy E Garber, Rong Fan, Kristie Bobolis, D Craig Allred, Joon Jeong, So Yeon Park, Franziska Michor, Kornelia Polyak
To investigate immune escape during breast tumor progression, we analyzed the composition of leukocytes in normal breast tissues, ductal carcinoma in situ (DCIS), and invasive ductal carcinomas (IDC). We found significant tissue and tumor subtype-specific differences in multiple cell types including T cells and neutrophils. Gene expression profiling of CD45+CD3+ T cells demonstrated a decrease in CD8+ signatures in IDCs. Immunofluorescence analysis showed fewer activated GZMB+CD8+ T cells in IDC than in DCIS, including in matched DCIS recurrent IDC...
June 26, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28648905/antibodies-against-immune-checkpoint-molecules-restore-functions-of-tumor-infiltrating-t-cells-in-hepatocellular-carcinomas
#8
Guoying Zhou, Dave Sprengers, Patrick P C Boor, Michail Doukas, Hannah Schutz, Shanta Mancham, Alexander Pedroza-Gonzalez, Wojciech G Polak, Jeroen de Jonge, Marcia Gaspersz, Haidong Dong, Kris Thielemans, Qiuwei Pan, Jan N M IJzermans, Marco J Bruno, Jaap Kwekkeboom
BACKGROUND & AIMS: Ligand binding to inhibitory receptors on immune cells, such as programmed cell death 1 (PD-1) and cytotoxic T-lymphocyte associated protein 4 (CTLA4), downregulates the T-cell-mediated immune response (called immune checkpoints). Antibodies that block these receptors increase anti-tumor immunity in patients with melanoma, non-small cell lung cancer, and renal cell cancer. Tumor-infiltrating CD4(+) and CD8(+) T cells in patients with hepatocellular carcinoma (HCC) have been found to be functionally compromised...
June 22, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28648363/dynamic-reorganization-of-chromatin-accessibility-signatures-during-dedifferentiation-of-secretory-precursors-into-lgr5-intestinal-stem-cells
#9
Unmesh Jadhav, Madhurima Saxena, Nicholas K O'Neill, Assieh Saadatpour, Guo-Cheng Yuan, Zachary Herbert, Kazutaka Murata, Ramesh A Shivdasani
Replicating Lgr5(+) stem cells and quiescent Bmi1(+) cells behave as intestinal stem cells (ISCs) in vivo. Disrupting Lgr5(+) ISCs triggers epithelial renewal from Bmi1(+) cells, from secretory or absorptive progenitors, and from Paneth cell precursors, revealing a high degree of plasticity within intestinal crypts. Here, we show that GFP(+) cells from Bmi1(GFP) mice are preterminal enteroendocrine cells and we identify CD69(+)CD274(+) cells as related goblet cell precursors. Upon loss of native Lgr5(+) ISCs, both populations revert toward an Lgr5(+) cell identity...
July 6, 2017: Cell Stem Cell
https://www.readbyqxmd.com/read/28633489/effects-of-early-pregnancy-on-uterine-lymphocytes-and-endometrial-expression-of-immune-regulatory-molecules-in-dairy-heifers1
#10
Sreelakshmi Vasudevan, Manasi M Kamat, Sadhat S Walusimbi, Joy L Pate, Troy L Ott
Natural killer (NK) cells are essential for establishment of human and rodent pregnancies. The function of these and other cytotoxic T cells (CTL) is controlled by stimulatory and inhibitory signaling. A role for cytotoxic cells during early pregnancy in cattle has not been described, but regulation of their function at the fetal-maternal interface is thought to be critical for conceptus survival. The hypothesis that the relative abundance of CTL and expression of inhibitory signaling molecules is increased by the conceptus during early pregnancy was tested...
June 19, 2017: Biology of Reproduction
https://www.readbyqxmd.com/read/28624577/identification-of-an-immune-specific-class-of-hepatocellular-carcinoma-based-on-molecular-features
#11
Daniela Sia, Yang Jiao, Iris Martinez-Quetglas, Olga Kuchuk, Carlos Villacorta-Martin, Manuel Castro de Moura, Juan Putra, Genis Camprecios, Laia Bassaganyas, Nicholas Akers, Bojan Losic, Samuel Waxman, Swan N Thung, Vincenzo Mazzaferro, Manel Esteller, Scott L Friedman, Myron Schwartz, Augusto Villanueva, Josep M Llovet
BACKGROUND & AIMS: Agents that induce an immune response against tumors by altering T-cell regulation have increased survival times of patients with advanced-stage tumors, such as melanoma or lung cancer. We aimed to characterize molecular features of immune cells that infiltrate hepatocellular carcinomas (HCCs) to determine whether these types of agents might be effective against liver tumors. METHODS: We analyzed HCC samples from 956 patients. We separated gene expression profiles from tumor, stromal, and immune cells using a non-negative matrix factorization algorithm...
June 15, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28581487/emmprin-cd147-is-induced-by-c-ebp%C3%AE-and-is-differentially-expressed-in-alk-and-alk-anaplastic-large-cell-lymphoma
#12
Janine Schmidt, Irina Bonzheim, Julia Steinhilber, Ivonne A Montes-Mojarro, Carlos Ortiz-Hidalgo, Wolfram Klapper, Falko Fend, Leticia Quintanilla-Martínez
Anaplastic lymphoma kinase-positive (ALK+) anaplastic large-cell lymphoma (ALCL) is characterized by expression of oncogenic ALK fusion proteins due to the translocation t(2;5)(p23;q35) or variants. Although genotypically a T-cell lymphoma, ALK+ ALCL cells frequently show loss of T-cell-specific surface antigens and expression of monocytic markers. C/EBPβ, a transcription factor constitutively overexpressed in ALK+ ALCL cells, has been shown to play an important role in the activation and differentiation of macrophages and is furthermore capable of transdifferentiating B-cell and T-cell progenitors to macrophages in vitro...
June 5, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/28579282/a-radiosensitivity-gene-signature-and-pd-l1-status-predict-clinical-outcome-of-patients-with-invasive-breast-carcinoma-in-the-cancer-genome-atlas-tcga-dataset
#13
Bum-Sup Jang, In Ah Kim
BACKGROUND AND PURPOSE: We investigated the link between the radiosensitivity gene signature and programmed cell death ligand 1 (PD-L1) status and clinical outcome in order to identify a group of patients that would possibly receive clinical benefit of radiotherapy (RT) combined with anti-PD1/PD-L1 therapy. MATERIAL AND METHODS: We validated the identified gene signature related to radiosensitivity and analyzed the PD-L1 status of invasive breast cancer in The Cancer Genome Atlas (TCGA) dataset...
June 1, 2017: Radiotherapy and Oncology: Journal of the European Society for Therapeutic Radiology and Oncology
https://www.readbyqxmd.com/read/28577136/genome-wide-gene-expression-profiling-reveals-that-cd274-is-up-regulated-new-onset-type-1-diabetes-mellitus
#14
Chen Fang, Yun Huang, Yufang Pei, Hong-Hong Zhang, Xiaohong Chen, Heming Guo, Sicheng Li, Xiaoyan Ji, Ji Hu
AIMS: Early studies have identified type 1 diabetes mellitus (T1DM) as a disease that is caused by the autoimmune destruction of the insulin-producing pancreatic β-cells. Genetics, environment and the immune pathogenesis of T1DM are three major pillars of T1DM research. We try to understand the changes in the gene expression profile during the pathogenesis of T1DM. METHODS: We performed a systematic search in the Gene Expression Omnibus (GEO) database for microarray studies of T1DM with samples taken at or before the T1DM onset...
June 2, 2017: Acta Diabetologica
https://www.readbyqxmd.com/read/28564607/specification-and-diversification-of-pericytes-and-smooth-muscle-cells-from-mesenchymoangioblasts
#15
Akhilesh Kumar, Saritha Sandra D'Souza, Oleg V Moskvin, Huishi Toh, Bowen Wang, Jue Zhang, Scott Swanson, Lian-Wang Guo, James A Thomson, Igor I Slukvin
Elucidating the pathways that lead to vasculogenic cells, and being able to identify their progenitors and lineage-restricted cells, is critical to the establishment of human pluripotent stem cell (hPSC) models for vascular diseases and development of vascular therapies. Here, we find that mesoderm-derived pericytes (PCs) and smooth muscle cells (SMCs) originate from a clonal mesenchymal progenitor mesenchymoangioblast (MB). In clonogenic cultures, MBs differentiate into primitive PDGFRβ(+)CD271(+)CD73(-) mesenchymal progenitors, which give rise to proliferative PCs, SMCs, and mesenchymal stem/stromal cells...
May 30, 2017: Cell Reports
https://www.readbyqxmd.com/read/28537924/genetic-defects-of-the-irf1-mediated-major-histocompatibility-complex-class-i-antigen-presentation-pathway-occur-prevalently-in-the-jak2-gene-in-non-small-cell-lung-cancer
#16
Tao Shen, Zhengming Chen, Zhizhuang Joe Zhao, Jie Wu
Recognition of major histocompatibility complex (MHC) class I antigens on tumor cells by cytotoxic T cells is involved in T cell-mediated tumor immune surveillance and immune checkpoint therapy. The interferon-γ (IFNγ)-IRF1 signaling pathway regulates MHC class I antigen presentation. To examine genetic defects of the IFNγ-IRF1 pathway in non-small cell lung cancer (NSCLC), we analyzed The Cancer Genome Atlas (TCGA) lung adenocarcinoma (LuAd) and lung squamous cell carcinoma (LuSc) data. Loss-of-function (LOF) genetic alterations of the IFNγ-IRF1 pathway genes (IFNGR1, IFNGR2, JAK1, JAK2, STAT1, IRF1) were found in 64 (6...
May 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28537889/immune-signature-of-metastatic-breast-cancer-identifying-predictive-markers-of-immunotherapy-response
#17
Ji-Yeon Kim, Eunjin Lee, Kyunghee Park, Woong-Yang Park, Hae Hyun Jung, Jin Seok Ahn, Young-Hyuck Im, Yeon Hee Park
In breast cancer (BC), up to 10-20% patients were known to have clinical benefit with immune checkpoint inhibitors, and biomarkers are needed for optimal use of this multi-potential therapeutic strategy. Accordingly, we conducted an experiment to identify expression of genes associated with immune checkpoints that represent potential targets of cancer immunotherapy. We performed whole-transcriptome sequencing and whole-exome sequencing using 37 refractory BC specimens. In the immune pathway gene set expression analysis, we found that HER2 expression and previous taxane treatment were positively correlated with high expression of immune gene set expression (p = 0...
July 18, 2017: Oncotarget
https://www.readbyqxmd.com/read/28527946/the-microbiome-and-hepatobiliary-pancreatic-cancers
#18
Kosuke Mima, Shigeki Nakagawa, Hiroshi Sawayama, Takatsugu Ishimoto, Katsunori Imai, Masaaki Iwatsuki, Daisuke Hashimoto, Yoshifumi Baba, Yo-Ichi Yamashita, Naoya Yoshida, Akira Chikamoto, Hideo Baba
The human intestinal microbiome encompasses at least 100 trillion microorganisms that can influence host immunity and disease conditions, including cancer. Hepatobiliary and pancreatic cancers have been associated with poor prognosis owing to their high level of tumor invasiveness, distant metastasis, and resistance to conventional treatment options, such as chemotherapy. Accumulating evidence from animal models suggests that specific microbes and microbial dysbiosis can potentiate hepatobiliary-pancreatic tumor development by damaging DNA, activating oncogenic signaling pathways, and producing tumor-promoting metabolites...
May 17, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28503213/epigenetic-modifications-of-the-immune-checkpoint-genes-ctla4-and-pdcd1-in-non-small-cell-lung-cancer-results-in-increased-expression
#19
Sebastian Marwitz, Swetlana Scheufele, Sven Perner, Martin Reck, Ole Ammerpohl, Torsten Goldmann
Targeting checkpoint inhibitors using monoclonal antibodies results in significantly better outcome of cancer patients compared to conventional chemotherapy. However, the current companion diagnostics to predict response is so far suboptimal, since they base on more or less reliable immunohistochemical approaches. In order to overcome these limitations, we analyzed epigenetic modifications of PDCD1 (PD1), CD274 (PD-L1), and CTLA4 in NSCLC tissues from 39 patients. Results were correlated with transcriptome data...
2017: Clinical Epigenetics
https://www.readbyqxmd.com/read/28491094/immunoprofiling-of-adult-derived-human-liver-stem-progenitor-cells-impact-of-hepatogenic-differentiation-and-inflammation
#20
Hoda El-Kehdy, Camillo Sargiacomo, Mohammad Fayyad-Kazan, Hussein Fayyad-Kazan, Catherine Lombard, Laurence Lagneaux, Etienne Sokal, Mehdi Najar, Mustapha Najimi
Adult-derived human liver stem/progenitor cells (ADHLSCs) are, nowadays, developed as therapeutic medicinal product for the treatment of liver defects. In this study, the impact of hepatogenic differentiation and inflammation priming on the ADHLSCs' immune profile was assessed in vitro and compared to that of mature hepatocytes. The constitutive immunological profile of ADHLSCs was greatly different from that of hepatocytes. Differences in the expression of the stromal markers CD90 and CD105, adhesion molecules CD44 and CD49e, immunoregulatory molecules CD73 and HO-1, and NK ligands CD112 and CD155 were noted...
2017: Stem Cells International
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