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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
#1
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
#2
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...
May 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28527946/the-microbiome-and-hepatobiliary-pancreatic-cancers
#3
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
#4
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
#5
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
https://www.readbyqxmd.com/read/28433800/chromosomal-alterations-and-gene-expression-changes-associated-with-the-progression-of-leukoplakia-to-advanced-gingivobuccal-cancer
#6
Priyanka G Bhosale, Simona Cristea, Srikant Ambatipudi, Rajiv S Desai, Rajiv Kumar, Asawari Patil, Shubhada Kane, Anita M Borges, Alejandro A Schäffer, Niko Beerenwinkel, Manoj B Mahimkar
We present an integrative genome-wide analysis that can be used to predict the risk of progression from leukoplakia to oral squamous cell carcinoma (OSCC) arising in the gingivobuccal complex (GBC). We find that the genomic and transcriptomic profiles of leukoplakia resemble those observed in later stages of OSCC and that several changes are associated with this progression, including amplification of 8q24.3, deletion of 8p23.2, and dysregulation of DERL3, EIF5A2, ECT2, HOXC9, HOXC13, MAL, MFAP5 and NELL2. Comparing copy number profiles of primary tumors with and without lymph-node metastasis, we identify alterations associated with metastasis, including amplifications of 3p26...
June 2017: Translational Oncology
https://www.readbyqxmd.com/read/28423491/the-mir-25-93-106b-cluster-regulates-tumor-metastasis-and-immune-evasion-via-modulation-of-cxcl12-and-pd-l1
#7
Michele Cioffi, Sara M Trabulo, Mireia Vallespinos, Deepak Raj, Tony Bou Kheir, Meng-Lay Lin, Julfa Begum, Ann-Marie Baker, Ala Amgheib, Jaimy Saif, Manuel Perez, Joaquim Soriano, Manuel Desco, Maria Victoria Gomez-Gaviro, Lorena Cusso, Diego Megias, Alexandra Aicher, Christopher Heeschen
The stromal microenvironment controls response to injury and inflammation, and is also an important determinant of cancer cell behavior. However, our understanding of its modulation by miRNA (miR) and their respective targets is still sparse. Here, we identified the miR-25-93-106b cluster and two new target genes as critical drivers for metastasis and immune evasion of cancer cells. Using miR-25-93-106b knockout mice or antagomiRs, we demonstrated regulation of the production of the chemoattractant CXCL12 controlling bone marrow metastasis...
March 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28409437/prognostic-significance-of-pd-l1-expression-on-tumor-cells-and-tumor-infiltrating-mononuclear-cells-in-upper-tract-urothelial-carcinoma
#8
Bo Zhang, Wei Yu, Xueru Feng, Zheng Zhao, Yu Fan, Yisen Meng, Shuai Hu, Yun Cui, Qun He, Hong Zhang, Dong Li, Zhisong He, Liqun Zhou, Jie Jin, Wenke Han
Immunotherapy targeting the programmed death-1 (PD-1) receptor/PD-1 ligand (PD-L1) pathway has shown promising results in several malignancies. However, the prognostic significance of PD-L1 expression remains unknown in patients with upper tract urothelial carcinoma (UTUC). This study aimed to evaluate PD-L1 expression and its association with clinicopathological characteristics and oncological outcomes in UTUC patients. PD-L1 expression on tumor cells and tumor-infiltrating mononuclear cells (TIMCs), and E-cadherin and N-cadherin expression on tumor cells were assessed by immunohistochemistry in a cohort of 162 patients with UTUC...
May 2017: Medical Oncology
https://www.readbyqxmd.com/read/28406723/aspirin-use-and-colorectal-cancer-survival-according-to-tumor-cd274-programmed-cell-death-1-ligand-1-expression-status
#9
Tsuyoshi Hamada, Yin Cao, Zhi Rong Qian, Yohei Masugi, Jonathan A Nowak, Juhong Yang, Mingyang Song, Kosuke Mima, Keisuke Kosumi, Li Liu, Yan Shi, Annacarolina da Silva, Mancang Gu, Wanwan Li, NaNa Keum, Xuehong Zhang, Kana Wu, Jeffrey A Meyerhardt, Edward L Giovannucci, Marios Giannakis, Scott J Rodig, Gordon J Freeman, Daniel Nevo, Molin Wang, Andrew T Chan, Charles S Fuchs, Reiko Nishihara, Shuji Ogino
Purpose Blockade of the programmed cell death 1 (PDCD1, PD-1) immune checkpoint pathway can improve clinical outcomes in various malignancies. Evidence suggests that aspirin (a widely used nonsteroidal anti-inflammatory drug) not only prolongs colorectal cancer survival, but can also activate T cell-mediated antitumor immunity and synergize with immunotherapy through inhibition of prostaglandin E2 production. We hypothesized that the survival benefit associated with aspirin might be stronger in colorectal carcinoma with a lower CD274 (PDCD1 ligand 1, PD-L1) expression level that resulted in lower signaling of the immune checkpoint pathway...
April 13, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28405764/prognostic-implication-of-cd274-pd-l1-protein-expression-in-tumor-infiltrating-immune-cells-for-microsatellite-unstable-and-stable-colorectal-cancer
#10
Kyu Sang Lee, Yoonjin Kwak, Soyeon Ahn, Eun Shin, Heung-Kwon Oh, Duck-Woo Kim, Sung-Bum Kang, Gheeyoung Choe, Woo Ho Kim, Hye Seung Lee
In this study, we investigated the clinical relevance of CD274 (PD-L1) protein expression by tumor cells and tumor-infiltrating immune cells in colorectal cancer (CRC). To this end, 186 microsatellite instability-high (MSI-H) and 153 microsatellite stable (MSS) CRCs were subjected to immunohistochemistry (IHC) analysis for the expression of CD274 and mismatch repair proteins. CD274 expression was evaluated in tumor cells at the center (TC) and periphery (TP), and immune cells at the center (IC) and periphery (IP) of CRC...
April 12, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28405504/pd-l1-cd274-copy-number-gain-expression-and-immune-cell-infiltration-as-candidate-predictors-for-response-to-immune-checkpoint-inhibitors-in-soft-tissue-sarcoma
#11
Jan Budczies, Gunhild Mechtersheimer, Carsten Denkert, Frederick Klauschen, Sadaf S Mughal, Priya Chudasama, Michael Bockmayr, Korinna Jöhrens, Volker Endris, Amelie Lier, Felix Lasitschka, Roland Penzel, Manfred Dietel, Benedikt Brors, Stefan Gröschel, Hanno Glimm, Peter Schirmacher, Marcus Renner, Stefan Fröhling, Albrecht Stenzinger
Soft-tissue sarcomas (STS) are rare malignancies that account for 1% of adult cancers and comprise more than 50 entities. Current therapeutic options for advanced-stage STS are limited. Immune checkpoint inhibitors targeting the PD-1/PD-L1 signaling axis are being explored as new treatment modality in STS; however, the determinants of response to these agents are largely unknown. Using the sarcoma data set of The Cancer Genome Altas (TCGA) and an independent cohort of untreated high-grade STS, we analyzed DNA copy number status and mRNA expression of PD-L1 in a total of 335 STS cases...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28400539/mass-cytometry-deep-phenotyping-of-human-mononuclear-phagocytes-and-myeloid-derived-suppressor-cells-from-human-blood-and-bone-marrow
#12
Mikael Roussel, P Brent Ferrell, Allison R Greenplate, Faustine Lhomme, Simon Le Gallou, Kirsten E Diggins, Douglas B Johnson, Jonathan M Irish
The monocyte phagocyte system (MPS) includes numerous monocyte, macrophage, and dendritic cell (DC) populations that are heterogeneous, both phenotypically and functionally. In this study, we sought to characterize those diverse MPS phenotypes with mass cytometry (CyTOF). To identify a deep phenotype of monocytes, macrophages, and DCs, a panel was designed to measure 38 identity, activation, and polarization markers, including CD14, CD16, HLA-DR, CD163, CD206, CD33, CD36, CD32, CD64, CD13, CD11b, CD11c, CD86, and CD274...
April 11, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28368722/tumor-cell-intrinsic-cd274-pd-l1-a-novel-metabolic-balancing-act-with-clinical-potential
#13
Curtis A Clark, Harshita B Gupta, Tyler J Curiel
Tumor expression of the immune co-signaling molecule CD274/PD-L1 was originally described as impeding antitumor immunity by direct engagement of its receptor, PDCD1/PD-1, on antitumor T cells. Melanoma-intrinsic PDCD1 was recently shown to promote tumor growth and MTOR signals in cooperation with tumor CD274, and sarcoma-intrinsic CD274 signaling promotes glucose metabolism to impede antitumor immunity. Our recent report shows that tumor cell-intrinsic CD274 promotes MTORC1 signaling in mouse melanoma and mouse and human ovarian cancer, inhibits autophagy and sensitizes some tumors to clinically available pharmacological autophagy inhibitors and confers resistance to MTOR inhibitors...
April 3, 2017: Autophagy
https://www.readbyqxmd.com/read/28363643/genetic-features-of-aflatoxin-associated-hepatocellular-carcinomas
#14
Weilong Zhang, Huan He, Mengya Zang, Qifeng Wu, Hong Zhao, Ling-Ling Lu, Peiqing Ma, Hongwei Zheng, Nengjin Wang, Ying Zhang, Siyuan He, Xiaoyan Chen, Zhiyuan Wu, Xiaoyue Wang, Jianqiang Cai, Zhihua Liu, Zongtang Sun, Yi-Xin Zeng, Chunfeng Qu, Yuchen Jiao
BACKGROUND & AIMS: Dietary exposure to aflatoxin is an important risk factor for hepatocellular carcinoma (HCC). However, little is known about the genomic features and mutations of aflatoxin-associated HCCs compared with HCCs not associated with aflatoxin exposure. We investigated the genetic features of aflatoxin-associated HCC that can be used to differentiate them from HCCs not associated with this carcinogen. METHODS: We obtained HCC tumor tissues and matched non-tumor liver tissues from 49 patients, collected from 1990 through 2016, at the Qidong Liver Cancer Hospital Institute in China-a high-risk region for aflatoxin exposure (38...
March 28, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28347512/characterization-of-immune-regulatory-molecules-b7-h4-and-pd-l1-in-low-and-high-grade-endometrial-tumors
#15
Amy Bregar, Amit Deshpande, Chris Grange, Tong Zi, Jennifer Stall, Heather Hirsch, Jason Reeves, Sriram Sathyanarayanan, Whitfield B Growdon, Bo R Rueda
BACKGROUND: The objective of this investigation was to characterize the expression landscape of immune regulatory molecules programmed death-ligand-1 (PD-L1, B7-H1) and B7-H4 in a cohort of endometrial tumors across the spectrum of grade and histology. MATERIALS AND METHODS: With institutional review board approval, 70 endometrial tumors from patients with known clinical outcomes were identified representing a spectrum of grade and histology. Immunohistochemistry (IHC) was performed for PD-L1 and B7-H4 and scored...
March 24, 2017: Gynecologic Oncology
https://www.readbyqxmd.com/read/28341226/lung-adenocarcinoma-and-squamous-cell-carcinoma-gene-expression-subtypes-demonstrate-significant-differences-in-tumor-immune-landscape
#16
Hawazin Faruki, Gregory M Mayhew, Jonathan S Serody, D Neil Hayes, Charles M Perou, Myla Lai-Goldman
INTRODUCTION: Molecular subtyping of lung adenocarcinoma (AD) and lung squamous cell carcinoma (SCC) reveal biologically diverse tumors that vary in their genomic and clinical attributes. METHODS: Published immune cell signatures and several lung AD and SCC gene expression data sets, including The Cancer Genome Atlas, were used to examine immune response in relation to AD and SCC expression subtypes. Expression of immune cell populations and other immune related genes, including CD274 molecule gene (CD274) (programmed death ligand 1), was investigated in the tumor microenvironment relative to the expression subtypes of the AD (terminal respiratory unit, proximal proliferative, and proximal inflammatory) and SCC (primitive, classical, secretory, and basal) subtypes...
March 21, 2017: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/28288138/muc1-c-integrates-pd-l1-induction-with-repression-of-immune-effectors-in-non-small-cell-lung-cancer
#17
A Bouillez, H Rajabi, C Jin, M Samur, A Tagde, M Alam, M Hiraki, T Maeda, X Hu, D Adeegbe, S Kharbanda, K-K Wong, D Kufe
Immunotherapeutic approaches, particularly programmed death 1/programmed death ligand 1 (PD-1/PD-L1) blockade, have improved the treatment of non-small-cell lung cancer (NSCLC), supporting the premise that evasion of immune destruction is of importance for NSCLC progression. However, the signals responsible for upregulation of PD-L1 in NSCLC cells and whether they are integrated with the regulation of other immune-related genes are not known. Mucin 1 (MUC1) is aberrantly overexpressed in NSCLC, activates the nuclear factor-κB (NF-κB) p65ZEB1 pathway and confers a poor prognosis...
March 13, 2017: Oncogene
https://www.readbyqxmd.com/read/28286742/persistent-exposure-to-porphyromonas-gingivalis-promotes-proliferative-and-invasion-capabilities-and-tumorigenic-properties-of-human-immortalized-oral-epithelial-cells
#18
Fengxue Geng, Junchao Liu, Yan Guo, Chen Li, Hongyang Wang, Hongyan Wang, Haijiao Zhao, Yaping Pan
Recent epidemiological studies revealed a significant association between oral squamous cell carcinoma (OSCC) and Porphyromonas gingivalis, a major pathogen of periodontal disease. As a keystone pathogen of periodontitis, P. gingivalis is known not only to damage local periodontal tissues, but also to evade the host immune system and eventually affect systemic health. However, its role in OSCC has yet to be defined. To explore the underlying effect of chronic P. gingivalis infection on OSCC and to identify relevant biomarkers as promising targets for therapy and prevention, we established a novel model by exposing human immortalized oral epithelial cells (HIOECs) to P...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/28249162/bet-bromodomain-inhibitors-engage-the-host-immune-system-and-regulate-expression-of-the-immune-checkpoint-ligand-pd-l1
#19
Simon J Hogg, Stephin J Vervoort, Sumit Deswal, Christopher J Ott, Jason Li, Leonie A Cluse, Paul A Beavis, Phillip K Darcy, Benjamin P Martin, Andrew Spencer, Anna K Traunbauer, Irina Sadovnik, Karin Bauer, Peter Valent, James E Bradner, Johannes Zuber, Jake Shortt, Ricky W Johnstone
BET inhibitors (BETi) target bromodomain-containing proteins and are currently being evaluated as anti-cancer agents. We find that maximal therapeutic effects of BETi in a Myc-driven B cell lymphoma model required an intact host immune system. Genome-wide analysis of the BETi-induced transcriptional response identified the immune checkpoint ligand Cd274 (Pd-l1) as a Myc-independent, BETi target-gene. BETi directly repressed constitutively expressed and interferon-gamma (IFN-γ) induced CD274 expression across different human and mouse tumor cell lines and primary patient samples...
February 28, 2017: Cell Reports
https://www.readbyqxmd.com/read/28243843/dynamic-gene-expression-analysis-in-a-h1n1-influenza-virus-mouse-pneumonia-model
#20
Yanyan Bao, Yingjie Gao, Yujing Shi, Xiaolan Cui
H1N1, a major pathogenic subtype of influenza A virus, causes a respiratory infection in humans and livestock that can range from a mild infection to more severe pneumonia associated with acute respiratory distress syndrome. Understanding the dynamic changes in the genome and the related functional changes induced by H1N1 influenza virus infection is essential to elucidating the pathogenesis of this virus and thereby determining strategies to prevent future outbreaks. In this study, we filtered the significantly expressed genes in mouse pneumonia using mRNA microarray analysis...
June 2017: Virus Genes
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