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Cancer immunity cycle

Christina Gutierrez Bracamontes, Rebecca Lopez-Valdez, Ramadevi Subramani, Arunkumar Arumugam, Sushmita Nandy, Venkatesh Rajamanickam, Vignesh Ravichandran, Rajkumar Lakshmanaswamy
Early parity reduces the risk of breast cancer in women while nulliparity and late parity increase the risk of breast cancer. In order to translate this protection to women where early pregnancy is not feasible, much work has focused on understanding how parity confers protection against breast cancer, the molecular mechanisms by which this occurs is still not well understood. Healthy parous and nulliparous women were recruited for this study. We assessed serum protein profiles of early parous, late parous, and nulliparous women using the Phospho Explorer antibody array...
October 19, 2016: Oncotarget
Sofia Sousa, Jorma Määttä
This overview addresses the recent research developments in the role of tumour-associated macrophages (TAM) in bone metastasis biology and management of breast and prostate cancer as well as in primary and lung metastatic osteosarcoma. Immunosuppressive M2-type TAMs have been shown to associate with poor prognosis. Throughout their life cycle, macrophages (Macs) can adapt to environmental cues and influence the surroundings by secreting different cytokines and enzymes crucial to matrix remodelling, infection fighting, immune regulation and/or inflammation...
September 2016: Journal of Bone Oncology
Troels Holz Borch, Lotte Engell-Noerregaard, Trine Zeeberg Iversen, Eva Ellebaek, Özcan Met, Morten Hansen, Mads Hald Andersen, Per Thor Straten, Inge Marie Svane
INTRODUCTION: Vaccination with dendritic cells (DCs) has generally not fulfilled its promise in cancer immunotherapy due to ineffective translation of immune responses into clinical responses. A proposed reason for this is intrinsic immune regulatory mechanisms, such as regulatory T cells (Tregs). A metronomic regimen of cyclophosphamide (mCy) has been shown to selectively deplete Tregs. To test this in a clinical setting, we conducted a phase I trial to evaluate the feasibility and safety of vaccination with DCs transfected with mRNA in combination with mCy in patients with metastatic malignant melanoma (MM)...
2016: Oncoimmunology
Ardeshir Kianercy, Kenneth J Pienta
Bone, which includes several cell populations and numerous cytokines and chemokines that provide cell-cell signaling, is a common destination for many cancer metastases. Bone metastasis skews this signaling to develop vicious cycles between immune, bone and cancer populations that lead to abnormal bone remodeling during cancer niche construction. Temporal models utilize positive feedback systems as an integrative tool providing insights into the rate-limiting processes that determine multiple stages of the bone metastasis...
2016: Advances in Experimental Medicine and Biology
Lin Li, Xiaotian Qi, Weili Sun, Hisham Abdel-Azim, Siyue Lou, Hong Zhu, Nemani V Prasadarao, Alice Zhou, Hiroyuki Shimada, Koichi Shudo, Yong-Mi Kim, Sajad Khazal, Qiaojun He, David Warburton, Lingtao Wu
Neutrophils generated by granulocyte colony-stimulating factor (GCSF) are functionally immature and, consequently, cannot effectively reduce infection and infection-related mortality in cancer chemotherapy-induced neutropenia (CCIN). Am80, a retinoic acid (RA) agonist that enhances granulocytic differentiation by selectively activating transcription factor RA receptor alpha (RARα), alternatively promotes RA-target gene expression. We found that in normal and malignant primary human hematopoietic specimens, Am80-GCSF combination coordinated proliferation with differentiation to develop complement receptor-3 (CR3)-dependent neutrophil innate immunity, through altering transcription of RA-target genes RARβ2, C/EBPε, CD66, CD11b, and CD18 This led to generation of functional neutrophils capable of fighting infection, whereas neutralizing neutrophil innate immunity with anti-CD18 antibody abolished neutrophil bactericidal activities induced by Am80-GCSF Further, Am80-GCSF synergy was evaluated using six different dose-schedule-infection mouse CCIN models...
October 13, 2016: EMBO Molecular Medicine
Miyeon Cho, Seok Won Jung, Soomin Lee, Kuwon Son, Gyu Hwan Park, Jong-Wha Jung, Yu Su Shin, Taegun Seo, Hyosun Cho, Hyojeung Kang
Kaposi's sarcoma-associated herpesvirus (KSHV) is a Gammaherpesvirus that causes acute infection and establishes life-long latency. KSHV causes several human cancers, including Kaposi's sarcoma, an acquired immune deficiency syndrome (AIDS)-related form of non-Hodgkin lymphoma. Genipin, an aglycone derived from geniposide found in Gardenia jasminoides, is known to be an excellent natural cross-linker, strong apoptosis inducer, and antiviral agent. Although evidence suggests antiviral activity of genipin in several in vitro viral infection systems, no inhibitory effect of genipin on KSHV infection has been reported...
2016: PloS One
Brian I Rini, Arnulf Stenzl, Romauld Zdrojowy, Mikhail Kogan, Mikhail Shkolnik, Stephane Oudard, Steffen Weikert, Sergio Bracarda, Simon J Crabb, Jens Bedke, Joerg Ludwig, Dominik Maurer, Regina Mendrzyk, Claudia Wagner, Andrea Mahr, Jens Fritsche, Toni Weinschenk, Steffen Walter, Alexandra Kirner, Harpreet Singh-Jasuja, Carsten Reinhardt, Tim Eisen
BACKGROUND: In a phase 2 study in patients with metastatic renal cell carcinoma, overall survival was associated with T-cell responses against IMA901, a vaccine consisting of ten tumour-associated peptides. In this phase 3 trial, we aimed to determine the clinical effect of adding IMA901 to sunitinib, the standard first-line treatment in metastatic renal cell carcinoma with postulated favourable immunomodulatory effects. METHODS: The IMPRINT study is an open-label, randomised, controlled, phase 3 trial done at 124 clinical sites in 11 countries...
October 3, 2016: Lancet Oncology
Kirollos S Hanna
PURPOSE: Pembrolizumab, a programmed cell death protein 1 (PD-1) inhibitor, is a humanized monoclonal antibody used in the treatment of metastatic or unresectable melanoma and advanced non-small cell lung cancer (NSCLC). We hereby report a case of pembrolizumab-induced uveitis to increase practitioner awareness. CASE REPORT: A 78-year-old female presented with onset of panuveitis after initiation of pembrolizumab therapy for metastatic melanoma. The patient received three cycles of therapy every 21 days during which her symptoms progressively worsened...
September 26, 2016: Pharmacotherapy
Marc O Johnson, Peter J Siska, Diana C Contreras, Jeffrey C Rathmell
T cells have dramatic functional and proliferative shifts in the course of maintaining immune protection from pathogens and cancer. To support these changes, T cells undergo metabolic reprogramming upon stimulation and again after antigen clearance. Depending on the extrinsic cell signals, T cells can differentiate into functionally distinct subsets that utilize and require diverse metabolic programs. Effector T cells (Teff) enhance glucose and glutamine uptake, whereas regulatory T cells (Treg) do not rely on significant rates of glycolysis...
October 3, 2016: Seminars in Immunology
Mariette Matondo, Marlène Marcellin, Karima Chaoui, Marie-Pierre Bousquet-Dubouch, Anne Gonzalez-de-Peredo, Bernard Monsarrat, Odile Burlet-Schiltz
The ubiquitin-proteasome pathway (UPP) plays a critical role in the degradation of proteins implicated in cell cycle control, signal transduction, DNA damage response, apoptosis and immune response. Proteasome inhibitors can inhibit the growth of a broad spectrum of human cancer cells by altering the balance of intracellular proteins. However, the targets of these compounds in acute myeloid leukemia (AML) cells have not been fully characterized. Herein, we combined large-scale quantitative analysis by SILAC-MS and targeted quantitative proteomic analysis in order to identify proteins regulated upon proteasome inhibition in two AML cell lines displaying different stages of maturation: immature KG1a cells and mature U937 cells...
October 6, 2016: Proteomics
Eileen E Parkes, Steven M Walker, Laura E Taggart, Nuala McCabe, Laura A Knight, Richard Wilkinson, Karen D McCloskey, Niamh E Buckley, Kienan I Savage, Manuel Salto-Tellez, Stephen McQuaid, Mary T Harte, Paul B Mullan, D Paul Harkin, Richard D Kennedy
BACKGROUND: Previously we identified a DNA damage response-deficient (DDRD) molecular subtype within breast cancer. A 44-gene assay identifying this subtype was validated as predicting benefit from DNA-damaging chemotherapy. This subtype was defined by interferon signaling. In this study, we address the mechanism of this immune response and its possible clinical significance. METHODS: We used immunohistochemistry (IHC) to characterize immune infiltration in 184 breast cancer samples, of which 65 were within the DDRD subtype...
January 2017: Journal of the National Cancer Institute
Junguo Wang, Fang Mei, Xia Gao, Shoulin Wang
Nasopharyngeal carcinoma (NPC) is the most common cancer originating from the nasopharynx, and can be induced by infection with Epstein-Barr virus (EBV). To study the mechanisms of EBV-associated NPC, a microarray of the GSE12452 dataset was analyzed. GSE12452 was downloaded from Gene Expression Omnibus and consisted of 31 NPC samples and 10 normal healthy nasopharyngeal tissue samples. The differentially-expressed genes (DEGs) were screened using the linear models for microarray data package in R. Using Database for Annotation, Visualization and Integrated Discovery software, potential functions of the DEGs were predicted by Gene Ontology and pathway enrichment analyses...
October 2016: Oncology Letters
Wenhui Yang, Yan He, Shijie Liu, Lulu Gan, Zhiguo Zhang, Jun Wang, Jie Liang, Yang Dong, Qing Wang, Zongliu Hou, Li Yang
Dysregulation of metabolism in hepatocytes leads to hepatic diseases such as hepatitis and non-alcoholic fatty liver disease (NAFLD). NAFLD represents a spectrum of liver diseases ranging from simple steatosis to nonalcoholic steatohepatitis (NASH). NASH is likely to progress to cirrhosis, liver failure and hepatocellular carcinoma, which lead to poor long-term prognosis. However, the exact mechanism of development of NAFLD is not well elucidated. In order to better understand the pathogenesis of NAFLD, we have performed an integrative analysis to livers from NAFLD rat models in a global view of the transcriptome...
September 30, 2016: Gene
Paul Zarogoulidis, Savvas Petanidis, Kalliopi Domvri, Efrosini Kioseoglou, Doxakis Anestakis, Lutz Freitag, Konstantinos Zarogoulidis, Wolfgang Hohenforst-Schmidt, Wilfried Eberhardt
Chemoresistance is a major challenge in lung cancer treatment. Recent findings have revealed that autophagic mechanism contributes significantly to immunosuppressive related chemoresistance. For that reason, targeting autophagy-related immunosuppression is an important approach to reverse tumor drug resistance. In this study, we report for the first time that autophagy inhibition triggers upregulation of CD4(+), Foxp3(+) tumor infiltrating lymphocytes in late metastatic lung cancer tissues. Furthermore, autophagy blockage induces chemosensitization to carboplatin, immune activation and cell cycle arrest...
September 16, 2016: Molecular Oncology
Krithiga Shridhar, Aastha Aggarwal, Gagandeep Kaur Walia, Smriti Gulati, A V Geetha, D Prabhakaran, Preet K Dhillon, Preetha Rajaraman
BACKGROUND: Oral cancers are preceded by oral potentially malignant disorders (OPMD). Understanding genetic susceptibility for OPMD risk could provide an opportunity for risk assessment of oral cancer through early disease course. We conducted a review of single nucleotide polymorphism (SNP) studies for OPMD risk. METHODS: We identified all relevant studies examining associations of SNPs with OPMD (leukoplakia, erythroplakia and oral sub-mucous fibrosis) conducted world-wide between January, 2000 and February, 2016 using a combined keyword search on PubMed...
October 2016: Oral Oncology
Emma Eriksson, Jessica Wenthe, Sandra Irenaeus, Angelica Loskog, Gustav Ullenhag
BACKGROUND: Cancer immunotherapy can be potentiated by conditioning regimens such as cyclophosphamide, which reduces the level of regulatory T cells (tregs). However, myeloid suppressive cells are still remaining. Accordingly to previous reports, gemcitabine improves immune status of cancer patients. In this study, the role of gemcitabine was further explored to map its immunological target cells and molecules in patients with pancreatic cancer. METHODS: Patient blood was investigated by flow cytometry and cytokine arrays at different time points during gemcitabine treatment...
September 29, 2016: Journal of Translational Medicine
P Xian, Y Li, H Zhou, H Luo, N Liu, J Y Dai
Objective: To evaluate the effect of Sunitinib therapy on immune function of patient with advanced renal cell carcinoma. Methods: A total of 27 patient with advanced renal cell carcinoma who received Sunitinib therapy in Chongqing Cancer Hospital from July 2010 to July 2014 were recruited in a prospective cohort study.Nineteen were male patients and 8 were female patients aged from 36 to 75 years with mean age of (58±7)years.Twenty-five cases were renal clear cell carcinoma, the other two cases were papillary renal cell carcinoma and Xp11...
October 1, 2016: Zhonghua Wai Ke za Zhi [Chinese Journal of Surgery]
Debora Fumagalli, David Venet, Michail Ignatiadis, Hatem A Azim, Marion Maetens, Françoise Rothé, Roberto Salgado, Ian Bradbury, Lajos Pusztai, Nadia Harbeck, Henry Gomez, Tsai-Wang Chang, Maria Antonia Coccia-Portugal, Serena Di Cosimo, Evandro de Azambuja, Lorena de la Peña, Paolo Nuciforo, Jan C Brase, Jens Huober, José Baselga, Martine Piccart, Sherene Loi, Christos Sotiriou
Importance: In neoadjuvant trials, treatment of human epidermal growth factor receptor 2 (HER2)-positive breast cancers with dual HER2 blockade resulted in increased pathologic complete response (pCR) rates compared with each targeted agent alone. Amplification and/or overexpression of HER2 currently remains the only biomarker for therapeutic decisions, but it is insufficient to explain the heterogeneous response to anti-HER2 agents. Objective: To investigate the ability of clinically and biologically relevant genes and gene signatures (GSs) measured by RNA sequencing to predict the efficacy of anti-HER2 agents...
September 29, 2016: JAMA Oncology
Fiona Day, Mahesh Kumar, Linda Fenton, Craig Gedye
A 72-year-old male patient was receiving second-line chemotherapy for metastatic squamous cell carcinoma of the skin (SCCS) when he was diagnosed with concurrent metastatic melanoma (BRAF mutant). Chemotherapy was ceased and he was treated with 4 cycles of ipilimumab immunotherapy. The patient experienced clinical benefit and durable remission in both malignancies and remains free of cancer progression 8 months after the last cycle of ipilimumab. Response of SCCS to ipilimumab has not been previously described, however this case and recent reports of pembrolizumab efficacy confirm the critical role of the immune system in SCCS pathogenesis and suggest further exploration of checkpoint immunotherapy for the treatment of this disease...
September 28, 2016: Journal of Immunotherapy
Leila Khoja, Eshetu G Atenafu, Arnoud Templeton, Ye Qye, Mary Anne Chappell, Sam Saibil, David Hogg, Marcus O Butler, Anthony M Joshua
Ipilimumab produces durable responses in some metastatic melanoma patients. Neutrophil, platelet, and eosinophil to lymphocyte ratios (NLR, PLR, and ELR) may be associated with the immune response in cancer thereby acting as biomarkers of toxicity and efficacy in ipilimumab-treated patients. Data were collected on clinical characteristics and lactate dehydrogenase (LDH), NLR, PLR, and ELR at baseline, post cycle 2 and at the end of treatment for 183 patients treated with ipilimumab between 2008 and 2015 at the Princess Margaret Cancer Centre...
September 29, 2016: Cancer Medicine
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