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interferon lung cancer

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https://www.readbyqxmd.com/read/29147627/stat1-gene-deficient-mice-develop-accelerated-breast-cancer-growth-and-metastasis-which-is-reduced-by-il-17-blockade
#1
Sanjay Varikuti, Steve Oghumu, Mohamad Elbaz, Greta Volpedo, Dinesh K Ahirwar, Pablo C Alarcon, Rachel H Sperling, Ellen Moretti, Marissa S Pioso, Jennifer Kimble, Mohd W Nasser, Ramesh K Ganju, Cesar Terrazas, Abhay R Satoskar
Signal transducer and activator of transcription 1 (STAT1) mediates interferon gamma signaling which activates the expression of various genes related to apoptosis, inflammation, cell cycle and angiogenesis. Several experimental and clinical studies have investigated the role of STAT1 in primary tumor growth in breast cancer; however, its role in tumor metastasis remains to be determined. To determine the role of STAT1 in breast cancer metastasis, we analyzed growth and metastasis in WT or STAT1(-/-) mice orthotopically implanted with metastatic 4T1...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/29124315/the-class-i-iv-hdac-inhibitor-mocetinostat-increases-tumor-antigen-presentation-decreases-immune-suppressive-cell-types-and-augments-checkpoint-inhibitor-therapy
#2
David Briere, Niranjan Sudhakar, David M Woods, Jill Hallin, Lars D Engstrom, Ruth Aranda, Harrah Chiang, Andressa L Sodré, Peter Olson, Jeffrey S Weber, James G Christensen
Checkpoint inhibitor therapy has led to major treatment advances for several cancers including non-small cell lung cancer (NSCLC). Despite this, a significant percentage of patients do not respond or develop resistance. Potential mechanisms of resistance include lack of expression of programmed death ligand 1 (PD-L1), decreased capacity to present tumor antigens, and the presence of an immunosuppressive tumor microenvironment. Mocetinostat is a spectrum-selective inhibitor of class I/IV histone deacetylases (HDACs), a family of proteins implicated in epigenetic silencing of immune regulatory genes in tumor and immune cells...
November 9, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/29123526/toll-like-receptor-ligands-and-interferon-%C3%AE-synergize-for-induction-of-antitumor-m1-macrophages
#3
Elisabeth Müller, Panagiotis F Christopoulos, Sanjib Halder, Anna Lunde, Kahsai Beraki, Martin Speth, Inger Øynebråten, Alexandre Corthay
Tumor-associated macrophages may either promote or suppress tumor growth depending on their activation status. Interferon-γ (IFN-γ) has been identified as a key factor for inducing tumoricidal M1 phenotype in macrophages. However, it remains unclear whether IFN-γ is sufficient or if additional stimuli are required. Here, we tested IFN-γ and a panel of toll-like receptor (TLR) agonists for the ability to activate murine macrophages toward a tumoricidal M1 phenotype. The following TLR ligands were used: TLR1/TLR2 agonist Pam3CSK4, TLR2/TLR6 agonist lipotechoic acid, TLR3 agonist poly(I:C), TLR4 agonist lipopolysaccharide (LPS), TLR5 agonist flagellin, TLR7 agonist CL264, and TLR9 agonist CpG...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29114547/predictive-factors-of-response-to-immunotherapy-a-review-from-the-spanish-melanoma-group-gem
#4
REVIEW
Enrique Espinosa, Ivan Márquez-Rodas, Ainara Soria, Alfonso Berrocal, Jose Luis Manzano, Maria Gonzalez-Cao, Salvador Martin-Algarra
Immunotherapy has become a key element in the treatment of several tumors, such as lung carcinoma and melanoma. Immunotherapy, unlike classical chemotherapy and targeted drugs, may yield long-term survival, even in patients who stop treatment due to toxicity. This fact has generated considerable excitement and a real shift in the paradigm of cancer treatment. However, only a small subset of patients benefit from immunotherapy. Survival curves show that most patients have progression of the disease in the first months after starting immunotherapy, followed by a slower decrease over the first 3 years, until curves reach a plateau...
October 2017: Annals of Translational Medicine
https://www.readbyqxmd.com/read/29100282/up-regulation-of-irf-3-expression-through-gata-1-acetylation-by-histone-deacetylase-inhibitor-in-lung-adenocarcinoma-a549-cells
#5
Lu-Lu Wang, Lan-Bo Zhou, Jin Shu, Nan-Nan Li, Hui-Wen Zhang, Rui Jin, Li-Li Zhuang, Guo-Ping Zhou
Interferon regulatory factor 3 (IRF-3) is an important transcription factor for interferon genes. Although its functional activation by viral infection has been widely explicated, the regulatory mechanism of IRF-3 gene expression in cancer cells is poorly understood. In this study, we demonstrated treatment of lung adenocarcinoma A549 cells with trichostatin A (TSA) and valproic acid (VPA), two different classes of histone deacetylase inhibitors, strongly stimulated IRF-3 gene expression. Truncated and mutated IRF-3 promoter indicated that a specific GATA-1 element was responsible for TSA-induced activation of IRF-3 promoter...
September 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/29100036/nafamostat-mesilate-a-serine-protease-inhibitor-suppresses-interferon-gamma-induced-up-regulation-of-programmed-cell-death-ligand-1-in-human-cancer-cells
#6
Sadamu Homma, Kazumi Hayashi, Kosaku Yoshida, Yukiko Sagawa, Yuko Kamata, Masaki Ito
Programmed cell death ligand-1 (PD-L1) plays a pivotal role in the suppression of antitumour immunity by binding to programmed cell death-1 (PD-1) on tumouricidal cytotoxic T lymphocytes (CTLs), rendering them inactive. As blockade of PD-1/PD-L1 interaction by the monoclonal antibodies induced effective T cell-mediated antitumour response, suppression of PD-L1 expression in tumour cells by the chemical agent might contribute to treatment against malignant tumours. Nafamostat mesilate (NM), a serine protease inhibitor that is frequently used in the clinic, potently suppressed interferon-gamma (IFN-gamma)-induced up-regulation of PD-L1 in cultured human lung cancer cells (HLC-1) at both the messenger RNA (mRNA) and protein levels...
October 28, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/29098034/asa404-a-vascular-disrupting-agent-as-an-experimental-treatment-approach-for-brain-tumors
#7
Oliver Bähr, Stefanie Gross, Patrick N Harter, Elmar Kirches, Christian Mawrin, Joachim P Steinbach, Michel Mittelbronn
Malignant brain tumors, including gliomas, brain metastases and anaplastic meningiomas, are associated with poor prognosis, and represent an unmet medical need. ASA404 (DMXAA), a vascular disrupting agent, has demonstrated promising results in several preclinical tumor models and early phase clinical trials. However, two phase III trials in non-small cell lung cancer reported insufficient results. The aim of the present study was to determine the effects of ASA404 on brain tumors. The effects of ASA404 were evaluated in vitro and in vivo using subcutaneous, and orthotopical models for malignant glioma (U-87, LN-229, U-251, LN-308 and Tu-2449), brain metastasis (HT-29) and malignant meningioma (IOMM-Lee)...
November 2017: Oncology Letters
https://www.readbyqxmd.com/read/29079845/glycolipid-peptide-conjugate-vaccines-enhance-cd8-t-cell-responses-against-human-viral-proteins
#8
M Speir, A Authier-Hall, C R Brooks, K J Farrand, B J Compton, R J Anderson, A Heiser, T L Osmond, C W Tang, J A Berzofsky, M Terabe, G F Painter, I F Hermans, R Weinkove
An important goal of vaccination against viruses and virus-driven cancers is to elicit cytotoxic CD8(+) T cells specific for virus-derived peptides. CD8(+) T cell responses can be enhanced by engaging help from natural killer T (NKT) cells. We have produced synthetic vaccines that induce strong peptide-specific CD8(+) T cell responses in vivo by incorporating an NKT cell-activating glycolipid. Here we examine the effect of a glycolipid-peptide conjugate vaccine incorporating an NKT cell-activating glycolipid linked to an MHC class I-restricted peptide from a viral antigen in human peripheral blood mononuclear cells...
October 27, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29025772/impaired-hla-class-i-antigen-processing-and-presentation-as-a-mechanism-of-acquired-resistance-to-immune-checkpoint-inhibitors-in-lung-cancer
#9
Scott Gettinger, Jungmin Choi, Katherine Hastings, Anna Truini, Ila Datar, Ryan Sowell, Anna Wurtz, Weilai Dong, Guoping Cai, Mary Ann Melnick, Victor Y Du, Joseph Schlessinger, Sarah B Goldberg, Anne Chiang, Miguel F Sanmamed, Ignacio Melero, Jackeline Agorreta, Luis M Montuenga, Richard Lifton, Soldano Ferrone, Paula Kavathas, David L Rimm, Susan M Kaech, Kurt A Schalper, Roy S Herbst, Katerina Politi
Mechanisms of acquired resistance to immune checkpoint inhibitors (ICIs) are poorly understood. We leveraged a collection of 14 ICI-resistant lung cancer samples to investigate whether alterations in genes encoding HLA Class I antigen processing and presentation machinery (APM) components or interferon signaling play a role in acquired resistance to PD-1 or PD-L1 antagonistic antibodies. Recurrent mutations or copy number changes were not detected in our cohort. In one case, we found acquired homozygous loss of B2M that caused lack of cell surface HLA class I expression in the tumor and a matched patient-derived xenograft (PDX)...
October 12, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28977839/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
#10
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...
September 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28962123/whole-genome-gene-expression-changes-and-hematological-effects-of-rikkunshito-in-patients-with-advanced-non-small-cell-lung-cancer-receiving-first-line-chemotherapy
#11
Yung-Che Chen, An-Shen Lin, Yu-Chiang Hung, Kuang-Den Chen, Ching-Yuan Wu, Chien-Hao Lie, Chang-Chun Hsiao, Chung-Jen Chen, Shih-Feng Liu, Wen-Feng Fang, Jen-Chieh Chang, Ting-Ya Wang, Yi-Hsi Wang, Yu-Hsiu Chung, Tung-Ying Chao, Sum-Yee Leung, Mao-Chang Su, Meng-Chih Lin
It has been demonstrated that the traditional Chinese medicine rikkunshito, ameliorates anorexia in several types of human cancer and attenuates lung injury by inhibiting neutrophil infiltration. The current study investigated the clinical and hematological effects of rikkunshito and its underlying mechanisms of action in the treatment of advanced non-small cell lung cancer (NSCLC). The Illumina microarray BeadChip was used to analyze the whole-genome expression profiles of peripheral blood mononuclear cells in 17 patients with advanced NSCLC...
September 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28950145/determination-of-poor-prognostic-immune-features-of-tumour-microenvironment-in-non-smoking-patients-with-lung-adenocarcinoma
#12
Tomonari Kinoshita, Chie Kudo-Saito, Reiko Muramatsu, Tomonobu Fujita, Miyuki Saito, Haruna Nagumo, Toshiharu Sakurai, Shinobu Noji, Emi Takahata, Tomonori Yaguchi, Nobuo Tsukamoto, Yuichiro Hayashi, Kaoru Kaseda, Ikuo Kamiyama, Takashi Ohtsuka, Kenji Tomizawa, Masaki Shimoji, Tetsuya Mitsudomi, Hisao Asamura, Yutaka Kawakami
We have previously demonstrated that the prognostic significance of tumour-infiltrating CD8(+) T cells significantly differs according to histological type and patient smoking habits in non-small cell lung cancer (NSCLC). This work suggested that infiltrating CD8(+) T cells may not be activated sufficiently in the immunosuppressive microenvironment in non-smokers with adenocarcinoma. To understand the immunogenic microenvironment in NSCLC, we characterised immune cells comprehensively by performing an immunohistochemical evaluation using an alternative counting method and multicolour staining method (n = 234), and assessed immune-related gene expression by using genetic analytical approaches (n = 58)...
September 23, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28932637/muc1-c-promotes-the-suppressive-immune-microenvironment-in-non-small-cell-lung-cancer
#13
Audrey Bouillez, Dennis Adeegbe, Caining Jin, Xiufeng Hu, Ashujit Tagde, Maroof Alam, Hasan Rajabi, Kwok-Kin Wong, Donald Kufe
The cancer immune microenvironment is of importance for the effectiveness of immunotherapy; however, its dysregulation is poorly understood. The MUC1-C oncoprotein is aberrantly overexpressed in non-small cell lung cancer (NSCLC) and has been linked to the induction of PD-L1. The present work investigated the effects of targeting MUC1-C in an immuno-competent MUC1 transgenic (MUC1.Tg) mouse model. We show that Lewis Lung Carcinoma cells expressing MUC1-C (LLC/MUC1) exhibit upregulation of PD-L1 and suppression of interferon-γ (IFN-γ)...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28930684/tumor-derived-mesenchymal-stem-cells-use-distinct-mechanisms-to-block-the-activity-of-natural-killer-cell-subsets
#14
Sabine Galland, Joanna Vuille, Patricia Martin, Igor Letovanec, Anne Caignard, Giulia Fregni, Ivan Stamenkovic
Mesenchymal stem cells (MSCs) display pleiotropic functions, which include secretion of soluble factors with immunosuppressive activity implicated in cancer progression. We compared the immunomodulatory effects on natural killer (NK) cells of paired intratumor (T)- and adjacent non-tumor tissue (N)-derived MSCs from patients with squamous cell lung carcinoma (SCC). We observed that T-MSCs were more strongly immunosuppressive than N-MSCs and affected both NK function and phenotype, as defined by CD56 expression...
September 19, 2017: Cell Reports
https://www.readbyqxmd.com/read/28914637/signal-transducer-and-activator-of-transcription-gain-of-function-primary-immunodeficiency-immunodysregulation-disorders
#15
Filippo Consonni, Laura Dotta, Francesca Todaro, Donatella Vairo, Raffaele Badolato
PURPOSE OF REVIEW: To describe primary immunodeficiencies caused by gain-of-function (GOF) mutations of signal transducer and activator of transcription (STAT) genes, a group of genetically determined disorders characterized by susceptibility to infections and, in many cases, autoimmune manifestations. RECENT FINDINGS: GOF mutations affecting STAT1 result in increased STAT tyrosine phosphorylation and secondarily increased response to STAT1-signaling cytokines, such as interferons...
December 2017: Current Opinion in Pediatrics
https://www.readbyqxmd.com/read/28904198/type-1-interferon-signalling-to-dendritic-cells-limits-murid-herpesvirus-4-spread-from-the-olfactory-epithelium
#16
Clara Lawler, Philip G Stevenson
Murid Herpesvirus-4 (MuHV-4) is a B cell-tropic gamma-herpesvirus that can be studied in vivo Despite viral evasion, type 1 interferons (IFN-I) limit its spread. After MuHV-4 inoculation into footpads, IFN-I protect lymph node subcapsular sinus macrophages (SSM) against productive infection; after peritoneal inoculation, they protect splenic marginal zone macrophages; and they limit MuHV-4 replication in the lungs. While invasive infections can test specific aspects of host colonization, it is important also to understand natural infection...
September 13, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28888924/mesothelin-specific-immune-responses-predict-survival-of-patients-with-brain-metastasis
#17
Liu Zhenjiang, Martin Rao, Xiaohua Luo, Elisabeth Sandberg, Jiri Bartek, Esther Schoutrop, Anna von Landenberg, Qingda Meng, Davide Valentini, Thomas Poiret, Georges Sinclair, Inti-Harvey Peredo, Ernest Dodoo, Markus Maeurer
BACKGROUND: Patients with advanced malignancies, e.g. lung cancer, ovarian cancer or melanoma, frequently present with brain metastases. Clinical presentation and disease progression of cancer is in part shaped by the interaction of the immune system with malignant cells. Antigen-targeted immune responses have been implicated in the prolonged survival of patients with cancer. This includes the tumor-associated antigen (TAA) mature mesothelin, a 40kDa cell surface-bound antigen that is overexpressed in several malignancies including lung ovarian and pancreatic cancer...
September 2017: EBioMedicine
https://www.readbyqxmd.com/read/28793935/utilization-of-electronic-health-record-events-to-conduct-a-tuberculosis-contact-investigation-in-a-high-risk-oncology-unit
#18
Shauna C Usiak, Fabian A Romero, Patrice Schwegman, Violet Fitzpatrick, MaryAnn Connor, Janet Eagan, Arthur E Brown, Mini Kamboj
OBJECTIVE To describe the utilization of electronic medical data resources, including health records and nursing scheduling resources, to conduct a tuberculosis (TB) exposure investigation in a high-risk oncology unit. SETTING A 42-bed inpatient unit with a mix of surgical and medical patients at a large tertiary-care cancer center in New York City. PARTICIPANTS High-risk subjects and coworkers exposed to a healthcare worker (HCW) with cavitary smear positive lung TB. RESULTS During the 3-month exposure period, 270 patients were admitted to the unit; 137 of these (50...
August 10, 2017: Infection Control and Hospital Epidemiology
https://www.readbyqxmd.com/read/28790504/cigarette-smoke-and-dna-cleavage-promote-lung-inflammation-and-emphysema
#19
Farrah Kheradmand, R You, Bon Hee Gu, D B Corry
Smoking-related lung diseases are among the most preventable and incurable ailments in the world. Smokers are at increased risk of developing chronic obstructive pulmonary disease that can be further complicated by emphysema and lung cancer. A subset of former smokers shows persistent lung inflammation and progressive loss of lung function, indicating a role for activation of acquired immunity in smoking-induced lung diseases. In addition to the well-established noxious effects of volatile compounds in cigarette smoke, incomplete combustion of tobacco generates nano-sized carbon black (nCB) that accumulate in lung myeloid dendritic cells and macrophages...
2017: Transactions of the American Clinical and Climatological Association
https://www.readbyqxmd.com/read/28761743/checkpoint-inhibitors-in-the-treatment-of-urological-malignancies
#20
REVIEW
Lazar S Popovic, Gorana Matovina-Brko, Maja Popovic
Checkpoint inhibitors are monoclonal antibodies attach to several different receptors on T-cells or tumour cells expressing receptors for cytotoxic T-lymphocyte antigen 4 (CTLA-4), programmed death-1 (PD-1) and their ligand (PD-L1). Since 2010, numerous trials on different tumour types have been conducted, which was resulted in these drugs being approved for the treatment of melanoma, lung cancer, Hodgkin's lymphoma and head and neck cancers. Urological cancers, especially urothelial and renal-cell carcinomas, are immunogenic tumours...
2017: ESMO Open
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