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Ovarian cancer cxcl10

Jan Budczies, Carsten Denkert, Balázs Győrffy, Peter Schirmacher, Albrecht Stenzinger
BACKGROUND: Inhibition of the PD-L1/PD-1 immune checkpoint axis represents one of the most promising approaches of immunotherapy for various cancer types. However, immune checkpoint inhibition is successful only in subpopulations of patients emphasizing the need for powerful biomarkers that adequately reflect the complex interaction between the tumor and the immune system. Recently, recurrent copy number gains (CNG) in chromosome 9p involving PD-L1 were detected in many cancer types including lung cancer, melanoma, bladder cancer, head and neck cancer, cervical cancer, soft tissue sarcoma, prostate cancer, gastric cancer, ovarian cancer, and triple-negative breast cancer...
December 6, 2017: BMC Medical Genomics
Alison L Van Dyke, Krystle A Lang Kuhs, Meredith S Shiels, Jill Koshiol, Britton Trabert, Erikka Loftfield, Mark P Purdue, Nicolas Wentzensen, Ruth M Pfeiffer, Hormuzd A Katki, Allan Hildesheim, Troy J Kemp, Ligia A Pinto, Anil K Chaturvedi, Mahboobeh Safaeian
Inflammation is increasingly thought to be associated with diabetes; however, only a few inflammation markers have been assessed concurrently in relation to history of diabetes. In the most comprehensive evaluation of inflammation markers and diabetes to date using a Luminex bead-based assay, we measured 78 inflammation-, immune-, and metabolic-related markers detectable in at least 10% of serum samples collected from participants from the Prostate, Lung, Colorectal and Ovarian Cancer (PLCO) screening trial (n = 1,814)...
2017: PloS One
Katrina K Au, Nichole Peterson, Peter Truesdell, Gillian Reid-Schachter, Kasra Khalaj, Runhan Ren, Julie-Ann Francis, Charles H Graham, Andrew W Craig, Madhuri Koti
OBJECTIVE: We recently established that high STAT1 expression and associated T helper type I tumour immune microenvironment (TME) are prognostic and chemotherapy response predictive biomarkers in high-grade serous ovarian cancer (HGSC). STAT1 induced chemokine CXCL10 is key to the recruitment of lymphocytes in the TME and is significantly highly expressed in the tumours from patients with longer survival. In the current study we therefore aimed to elucidate the role CXCL10 in disease progression and tumour immune transcriptomic alterations using the ID8 syngeneic murine model of HGSC...
June 2017: Gynecologic Oncology
Katrina K Au, Cécile Le Page, Runhan Ren, Liliane Meunier, Isabelle Clément, Kathrin Tyrishkin, Nichole Peterson, Jennifer Kendall-Dupont, Timothy Childs, Julie-Ann Francis, Charles H Graham, Andrew W Craig, Jeremy A Squire, Anne-Marie Mes-Masson, Madhuri Koti
High-grade serous ovarian carcinoma (HGSC) accounts for 70% of all epithelial ovarian cancers but clinical management is challenged by a lack of accurate prognostic and predictive biomarkers of chemotherapy response. This study evaluated the role of Signal Transducer and Activator of Transcription 1 (STAT1) as an independent prognostic and predictive biomarker and its correlation with intratumoural CD8(+) T cells in a second independent biomarker validation study. Tumour STAT1 expression and intratumoural CD8(+) T cell infiltration were assessed by immunohistochemistry as a multicentre validation study conducted on 734 chemotherapy-naïve HGSCs...
October 2016: Journal of Pathology. Clinical Research
Holger Bronger, Judith Singer, Claudia Windmüller, Ute Reuning, Daniela Zech, Claire Delbridge, Julia Dorn, Marion Kiechle, Barbara Schmalfeldt, Manfred Schmitt, Stefanie Avril
BACKGROUND: Tumour-infiltrating lymphocytes (TILs) are associated with improved survival in several epithelial cancers. The two chemokines CXCL9 and CXCL10 facilitate chemotactic recruitment of TILs, and their intratumoral accumulation is a conceivable way to improve TIL-dependent immune intervention in cancer. However, the prognostic impact of CXCL9 and CXCL10 in high-grade serous ovarian cancer (HGSC) is largely unknown. METHODS: One hundred and eighty four cases of HGSC were immunohistochemically analyzed for CXCL9, CXCL10...
August 23, 2016: British Journal of Cancer
Dongjun Peng, Ilona Kryczek, Nisha Nagarsheth, Lili Zhao, Shuang Wei, Weimin Wang, Yuqing Sun, Ende Zhao, Linda Vatan, Wojciech Szeliga, Jan Kotarski, Rafał Tarkowski, Yali Dou, Kathleen Cho, Sharon Hensley-Alford, Adnan Munkarah, Rebecca Liu, Weiping Zou
Epigenetic silencing including histone modifications and DNA methylation is an important tumorigenic mechanism. However, its role in cancer immunopathology and immunotherapy is poorly understood. Using human ovarian cancers as our model, here we show that enhancer of zeste homologue 2 (EZH2)-mediated histone H3 lysine 27 trimethylation (H3K27me3) and DNA methyltransferase 1 (DNMT1)-mediated DNA methylation repress the tumour production of T helper 1 (TH1)-type chemokines CXCL9 and CXCL10, and subsequently determine effector T-cell trafficking to the tumour microenvironment...
November 12, 2015: Nature
Emese Zsiros, Priyanka Duttagupta, Denarda Dangaj, Hongzhe Li, Renee Frank, Thomas Garrabrant, Ian S Hagemann, Bruce L Levine, Carl H June, Lin Zhang, Ena Wang, Francesco M Marincola, Davide Bedognetti, Daniel J Powell, Janos Tanyi, Michael D Feldman, Lana E Kandalaft, George Coukos
PURPOSE: Chemokines are implicated in T-cell trafficking. We mapped the chemokine landscape in advanced stage ovarian cancer and characterized the expression of cognate receptors in autologous dendritic cell (DC)-vaccine primed T cells in the context of cell-based immunotherapy. EXPERIMENTAL DESIGN: The expression of all known human chemokines in patients with primary ovarian cancer was analyzed on two independent microarray datasets and validated on tissue microarray...
June 15, 2015: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Cari M Kitahara, Britton Trabert, Hormuzd A Katki, Anil K Chaturvedi, Troy J Kemp, Ligia A Pinto, Steven C Moore, Mark P Purdue, Nicolas Wentzensen, Allan Hildesheim, Meredith S Shiels
BACKGROUND: Epidemiologic studies examining circulating levels of inflammatory markers in relation to obesity and physical inactivity may aid in our understanding of the role of inflammation in obesity-related cancers. However, previous studies on this topic have focused on a limited set of markers. METHODS: We evaluated associations between body mass index (BMI) and vigorous physical activity level, based on self-report, and serum levels of 78 inflammation-related markers...
December 2014: Cancer Epidemiology, Biomarkers & Prevention
Jeffrey L Wong, Erik Berk, Robert P Edwards, Pawel Kalinski
Chemokine-driven interactions of immune cells are essential for effective antitumor immunity. Human natural killer (NK) cells can be primed by the interleukin (IL)-1-related proinflammatory cytokine IL-18 for unique helper activity, which promotes dendritic cell (DC) activation and DC-mediated induction of type-1 immune responses against cancer. Here, we show that such IL-18-primed "helper" NK cells produce high levels of the immature DC (iDC)-attracting chemokines CCL3 and CCL4 upon exposure to tumor cells or the additional inflammatory signals IFN-α, IL-15, IL-12, or IL-2...
August 1, 2013: Cancer Research
Adam Rainczuk, Jyothsna Rao, Jessica Gathercole, Andrew N Stephens
In recent years, chemokines have generated intense investigations due to their involvement in both physiological and pathological processes of inflammation, particularly in ovarian biology. The physiological process of ovulation in the normal ovary involves various chemokines that mediate the healing of the ruptured endometrium. It is now being reported that many of these chemokines are also associated with the cancer of the ovary. Chronic inflammation underlies the progression of ovarian cancer; therefore, it raises the possibility that chemokines are involved in the inflammatory process and mediate immune responses that may favour or inhibit tumour progression...
September 2012: Reproduction: the Official Journal of the Society for the Study of Fertility
Fan Yang, Malin Gou, Hongxin Deng, Tao Yi, Qian Zhong, Yuquan Wei, Xia Zhao
Currently, great interest is focused on the anti-neoplastic effects of CXC chemokine ligand 10 (IP-10/CXCL10). IP-10 has shown significant antitumor and anti-metastatic properties via immunological, antiangiogenic and anti-neoplastic mechanisms. However, very few studies on the antitumor activity of IP-10 in human ovarian cancer have been reported. The use of polymeric nanoparticles to deliver functional genes intraperitoneally holds much promise as an effective therapy for ovarian cancer. In our study, a recombinant plasmid expressing IP-10 (pVITRO-IP-10) was constructed, and biodegradable cationic heparin-polyethyleneimine (HPEI) nanogels were prepared to deliver pVITRO-IP-10 into SKOV3 human ovarian cancer cells...
August 2012: Oncology Reports
Kirsten Kübler, Carola tho Pesch, Nadine Gehrke, Soheila Riemann, Juliane Dassler, Christoph Coch, Jennifer Landsberg, Vera Wimmenauer, Martin Pölcher, Christian Rudlowski, Thomas Tüting, Walther Kuhn, Gunther Hartmann, Winfried Barchet
Owing to high rates of tumor relapse, ovarian cancer remains a fatal disease for which new therapeutic approaches are urgently needed. Accumulating evidence indicates that immune stimulation may delay or even prevent disease recurrence in ovarian cancer. In order to elicit proinflammatory signals that induce or amplify antitumor immune reactivity, we mimicked viral infection in ascites-derived ovarian cancer cells. By transfection or electroporation we targeted the synthetic double-stranded RNA poly(I:C) intracellularly in order to activate melanoma differentiation-associated gene-5 (MDA-5), a sensor of viral RNA in the cytosol of somatic cells...
October 2011: European Journal of Immunology
Kirsten Kübler, Nadine Gehrke, Soheila Riemann, Volker Böhnert, Thomas Zillinger, Evelyn Hartmann, Martin Pölcher, Christian Rudlowski, Walther Kuhn, Gunther Hartmann, Winfried Barchet
Most malignant cells are poorly immunogenic and fail to elicit an effective antitumor immune response. In contrast, viral infections of cells are promptly detected and eliminated by the immune system. Viral recognition critically hinges on cytosolic nucleic acid receptors that include the proinflammatory RNA helicase retinoic acid-inducible gene-I (RIG-I). Here, we show that targeted delivery of RIG-I agonists induced ovarian cancer cells to upregulate HLA class I and to secrete the proinflammatory cytokines CXCL10, CCL5, interleukin-6, tumor necrosis factor-alpha, and IFN-beta...
July 1, 2010: Cancer Research
Seth B Coffelt, Suzanne L Tomchuck, Kevin J Zwezdaryk, Elizabeth S Danka, Aline B Scandurro
Emerging evidence suggests that the antimicrobial peptide, leucine leucine-37 (LL-37), could play a role in the progression of solid tumors. LL-37 is expressed as the COOH terminus of human cationic antimicrobial protein-18 (hCAP-18) in ovarian, breast, and lung cancers. Previous studies have shown that the addition of LL-37 to various cancer cell lines in vitro stimulates proliferation, migration, and invasion. Similarly, overexpression of hCAP-18/LL-37 in vivo accelerates tumor growth. However, the receptor or receptors through which these processes are mediated have not been thoroughly examined...
June 2009: Molecular Cancer Research: MCR
Ilona Kryczek, Mousumi Banerjee, Pui Cheng, Linhua Vatan, Wojciech Szeliga, Shuang Wei, Emina Huang, Emily Finlayson, Diane Simeone, Theodore H Welling, Alfred Chang, George Coukos, Rebecca Liu, Weiping Zou
Th17 cells play an active role in autoimmune diseases. However, the nature of Th17 cells is poorly understood in cancer patients. We studied Th17 cells, the associated mechanisms, and clinical significance in 201 ovarian cancer patients. Tumor-infiltrating Th17 cells exhibit a polyfunctional effector T-cell phenotype, are positively associated with effector cells, and are negatively associated with tumor-infiltrating regulatory T cells. Tumor-associated macrophages promote Th17 cells through interleukin-1beta (IL-1beta), whereas tumor-infiltrating regulatory T cells inhibit Th17 cells through an adenosinergic pathway...
August 6, 2009: Blood
Jamie M Heinzman, Stacey L Brower, Jason E Bush
BACKGROUND: A localized hypoxic environment occurs during tumor growth necessitating an angiogenic response or tumor necrosis results. Novel cancer treatment strategies take advantage of tumor-induced vascularisation by combining standard chemotherapeutic agents with angiogenesis-inhibiting agents. This has extended the progression-free interval and prolonged survival in patients with various types of cancer. We postulated that the expression levels of angiogenesis-related proteins from various primary tumor cultures would be greater under hypoxic conditions than under normoxia...
2008: Cancer Cell International
Jing Wang, Chang-Qing Zhang, Juan Liu, Li-Hua Sui
BACKGROUND & OBJECTIVE: The incidence, recurrence rate, and metastasis rate of malignant ovarian tumors are high. Interleukin-12 (IL-12) has antitumor effect. This study was to investigate the effects of IL-12 on the proliferation of human ovarian carcinoma SKOV3 cells in vitro and in vivo. METHODS: The plasmid containing mouse IL-12 gene was transfected into SKOV3 cells (SKOV3/IL-12). Blank plasmid-transfected SKOV3 cells (SKOV3/neo) and untransfected SKOV3 cells were used as controls...
December 2007: Ai Zheng, Aizheng, Chinese Journal of Cancer
Deok-Soo Son, Angelika K Parl, Valerie Montgomery Rice, Dineo Khabele
Chronic inflammation is an important underlying condition for ovarian tumor development, growth and progression. Since chemokine networks are activated by inflammation, patterns of chemokine gene expression were investigated in ovarian cancer cells. Chemokine specific microarrays were performed after mouse (ID8) and human (SKOV-3) ovarian surface epithelial cancer cells were exposed to the inflammatory agent bacterial endotoxin lipopolysaccharide (LPS, 10 microg/ml) and pro-inflammatory cytokines interleukin-1beta (IL-1, 10 ng/ml) and tumor necrosis factor-alpha (TNF, 10 ng/ml)...
August 2007: Cancer Biology & Therapy
Charlotta Dabrosin
Angiogenesis is essential for normal function in the female reproductive tract and a prerequisite for growth and metastasis of solid tumors. Several factors, both inducers and inhibitors, play essential roles in the regulation of the angiogenic process. Exposure to sex steroids increases the risk of breast cancer but the mechanisms are poorly understood and the importance of angiogenesis in breast carcinogenesis is undefined. In the female reproductive tract ovarian hormones tightly regulate angiogenesis. The breast is also a target organ for sex steroids but very little is known about sex steroid effects on angiogenesis in normal breast tissue and breast cancer...
2005: Angiogenesis
G E Peoples, B W Anderson, T V Lee, J L Murray, A P Kudelka, J T Wharton, C G Ioannides
The immune system can be efficiently stimulated and targeted to specific antigens expressed exclusively or preferentially by experimental cancers. The foremost limitations to extending this vaccine technology to the prevalent epithelial-derived cancers are the lack of: (a) identified tumor-associated antigens recognized by cellular immunity; (b) antigens expressed on the majority of tumor cells during disease progression; and (c) immunogenic CTL epitopes. To date, only HER-2/neu has been shown to be the source of naturally occurring, MHC-restricted, CTL-recognized peptides in epithelial tumors...
December 1999: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
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