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Tumor microenviroment

George C Prendergast, William J Malachowski, Arpita Mondal, Peggy Scherle, Alexander J Muller
The tryptophan catabolic enzyme indoleamine 2,3-dioxygenase-1 (IDO1) has attracted enormous attention in driving cancer immunosuppression, neovascularization, and metastasis. IDO1 suppresses local CD8+ T effector cells and natural killer cells and induces CD4+ T regulatory cells (iTreg) and myeloid-derived suppressor cells (MDSC). The structurally distinct enzyme tryptophan dioxygenase (TDO) also has been implicated recently in immune escape and metastatic progression. Lastly, emerging evidence suggests that the IDO1-related enzyme IDO2 may support IDO1-mediated iTreg and contribute to B-cell inflammed states in certain cancers...
2018: International Review of Cell and Molecular Biology
Shulin Wu, Jianheng Ye, Zongwei Wang, Sharron X Lin, Min Lu, Yingke Liang, Xuejin Zhu, Aria F Olumi, Wei-de Zhong, Chin-Lee Wu
Putative gender differences in bladder cancer (BCa) have been proposed to result from sex hormone influence. Aromatase is the key enzyme catalyzing the conversion of androgens to estrogens which may result in an intratumoral microenviroment with increased estrogen production. In this study, we investigated the expression pattern of aromatase and its association with BCa progression. Tissue samples from 88 BCa patients who underwent cystectomy were obtained. Using immunohistochemistry (IHC), expression of aromatase in tumor epithelium (TE) and tumor related stroma (TS) were evaluated separately, and the association of aromatase expression status with pathologic variables and overall survival (OS) outcome was examined...
January 5, 2018: Cancer Biology & Therapy
Jing-Bo Yang, Zhi-Bin Zhao, Qing-Zhi Liu, Tai-Dou Hu, Jie Long, Kai Yan, Zhe-Xiong Lian
Macrophages are a critical component in host immune responses against tumor. In this work we investigated the role of forkhead box O1 (FoxO1) in the transcriptional regulation in macrophages, which affects the anti-tumor functions of tumor-associated macrophages (TAMs). First, we showed that TAMs expressed reduced levels of FoxO1, which was associated with their protumoral M2 polarization state. The suppression of FoxO1 expression in TAM was induced by the hypoxic condition in the tumor microenviroment. Next, we confirmed that FoxO1 positively regulates MHC-II genes by binding to the promoter region of Ciita gene, the master activator of multiple MHC-II genes...
December 14, 2017: Oncogene
Gerben R Borst, Ramya Kumareswaran, Hatice Yücel, Seyda Telli, Trevor Do, Trevor McKee, Gaetano Zafarana, Jos Jonkers, Marcel Verheij, Mark J O'Connor, Sven Rottenberg, Robert G Bristow
Clinical trials are studying the benefits of combining the PARP-1 inhibitor olaparib with chemotherapy and radiotherapy treatment in a variety of cancer increasing the therapeutic ratio for olaparib may come from its ability to modify the tumour microenvironment by targeting homologous recombination-deficient, hypoxic tumour clonogens, and/or increasing tumour-associated vasodilation to improve oxygenation. Herein, we investigated the effect of prolonged neoadjuvant exposure to olaparib on the tumor microenvironment using a genetically-engineered mouse p53-/- syngeneic breast cancer model, which is proficient in homology-directed DNA repair...
October 20, 2017: Oncotarget
Joseph A Sparano, Robert Gray, Maja H Oktay, David Entenberg, Thomas Rohan, Xiaonan Xue, Michael Donovan, Michael Peterson, Anthony Shuber, Douglas A Hamilton, Timothy D'Alfonso, Lori J Goldstein, Frank Gertler, Nancy E Davidson, John Condeelis, Joan Jones
Metastasis is the primary cause of death in early-stage breast cancer. We evaluated the association between a metastasis biomarker, which we call "Tumor Microenviroment of Metastasis" (TMEM), and risk of recurrence. TMEM are microanatomic structures where invasive tumor cells are in direct contact with endothelial cells and macrophages, and which serve as intravasation sites for tumor cells into the circulation. We evaluated primary tumors from 600 patients with Stage I-III breast cancer treated with adjuvant chemotherapy in trial E2197 (NCT00003519), plus endocrine therapy for hormone receptor (HR)+ disease...
2017: NPJ Breast Cancer
Massimiliano Mazzone, Alessio Menga, Alessandra Castegna
From the evidence on clinical studies and experimental mouse models we now know that tumor associated macrophages (TAMs) sustain tumor development in many different ways. They play a role in angiogenesis, tumor cell invasion and metastasis formation. Additionally, TAMs interfere with natural killer and T cell antitumoral activities, producing an immune suppressive environment that protects tumor cell growth. This indicates that the tumoricidal activity of macrophages within the tumor microenviroment is lost due to an imbalance of the regulatory mechanisms underpinning these cells' function...
October 21, 2017: FEBS Journal
Guobin Zhang, Yunsheng Zhang, Sen Cheng, Zhen Wu, Fusheng Liu, Junting Zhang
Hypoxia is a major regulator of glioma development and aggressiveness. However, how CD133 positive U87 glioblastoma cells adapt to hypoxia and communicate with their surrounding microenvironment during tumor development remain important questions. Communication with host cells and stroma via exosomes represents one pathway by which tumors can modify their surroundings to achieve a tumor-permissive environment. MicroRNAs are thought to be essential actors of tumorigenesis as they are able to control the expression of numerous genes...
October 2017: Journal of Neuro-oncology
Michael J Nathenson, Anthony P Conley, Edward Sausville
Soft tissue and bone sarcomas are a rare and heterogeneous form of cancer. With standard of care treatment options including surgery, radiation, and chemotherapy, the long-term survival is still low for high-risk soft tissue sarcoma patients. New treatment strategies are needed. Immunotherapy offers a new potential treatment paradigm with great promise. Immunotherapy of soft tissue sarcomas dates back to Dr. Coley's first use of toxins in the late 1800s. A variety of strategies of immunotherapy have been tried in soft tissue and bone sarcomas, including various vaccines and cytokines, with limited success...
September 21, 2017: Oncologist
D Yu, X M Qi, X Zhao, Y Liu, K Xue, C S Jin, L J Wen
T cell immune checkpoint pathways contribute to tumor immune escape. Many studies have shown that immune checkpoint is demonstrably correlated with tumor grade or prognosis in several types of malignancies and immune checkpoint has become a new biological index for tumor detection and prognosis. Immune checkpoint inhibitors have shown promising tumor outcomes in clinical trials for some advanced solid tumors and it will become a new target for cancer immunotherapy. In this review we will explore the correlation between expressions of immune checkpoint-associated genes and proteins in immune microenviroment and prognosis of head and neck squamous cell carcinoma, and specifically will discuss how this pathway can be manipulated with immune therapeutic drugs...
September 7, 2017: Zhonghua Er Bi Yan Hou Tou Jing Wai Ke za Zhi, Chinese Journal of Otorhinolaryngology Head and Neck Surgery
Thiago M Bianco, Douglas R Abdalla, Chamberttan S Desidério, Sofie Thys, Cindy Simoens, John-Paul Bogers, Eddie F C Murta, Márcia A Michelin
This study aimed to investigate the influence of physical activity in innate immunity to conduce to an effective antitumoral immune response analyzing the phenotype and activation status of infiltrating cells. We analysed the intracellular cytokines and the transcription factors of tumor infiltrating lymphocytes (TILS) and spleen leukocytes. The Nos2 gene expression was evaluated in spleen cells and futhermore the ROS production was measured and spleen cells; another cell evaluated was dendritic cells (TIDCs), their cytokines expression and membrane molecules; finally to understood the results obtained, we analysed the dendritic cells obtained from bone marrow...
August 14, 2017: Immunology Letters
Christos Vaklavas, Scott W Blume, William E Grizzle
Although transcript levels have been traditionally used as a surrogate measure of gene expression, it is increasingly recognized that the latter is extensively and dynamically modulated at the level of translation (messenger RNA to protein). Over the recent years, significant progress has been made in dissecting the complex posttranscriptional mechanisms that regulate gene expression. This advancement in knowledge came hand in hand with the progress made in the methodologies to study translation both at gene-specific as well as global genomic level...
2017: Frontiers in Oncology
Vincenzo Borgna, Jaime Villegas, Verónica A Burzio, Sebastián Belmar, Mariela Araya, Emanuel Jeldes, Lorena Lobos-González, Verónica Silva, Claudio Villota, Luciana Oliveira-Cruz, Constanza Lopez, Teresa Socias, Octavio Castillo, Luis O Burzio
Knockdown of antisense noncoding mitochondrial RNAs (ASncmtRNAs) induces apoptosis in several human and mouse tumor cell lines, but not normal cells, suggesting this approach for a selective therapy against different types of cancer. Here we show that in vitro knockdown of murine ASncmtRNAs induces apoptotic death of mouse renal adenocarcinoma RenCa cells, but not normal murine kidney epithelial cells. In a syngeneic subcutaneous RenCa model, treatment delayed and even reversed tumor growth. Since the subcutaneous model does not reflect the natural microenviroment of renal cancer, we used an orthotopic model of RenCa cells inoculated under the renal capsule...
July 4, 2017: Oncotarget
Aline Lopes Ribeiro, Carolini Kaid, Patrícia B G Silva, Beatriz A Cortez, Oswaldo Keith Okamoto
Pericytes are important cellular components of the tumor microenviroment with established roles in angiogenesis and metastasis. These two cancer hallmarks are modulated by enzymes of the LOX family, but thus far, information about LOX relevance in tumor-associated pericytes is lacking. Here, we performed a comparative characterization of normal and tumoral pericytes and report for the first time the modulatory effects of LOX enzymes on activated pericyte properties. Tumoral pericytes isolated from childhood ependymoma and neuroblastoma specimens displayed angiogenic properties in vitro and expressed typical markers, including CD146, NG2, and PDGFRβ...
2017: Stem Cells International
Yang Wang, Kazuki Takeishi, Zhao Li, Eduardo Cervantes-Alvarez, Alexandra Collin de l'Hortet, Jorge Guzman-Lepe, Xiao Cui, Jiye Zhu
Organ-like microenviroment and 3-dimensional (3D) cell culture conformations have been suggested as promising approaches to mimic in a micro-scale a whole organ cellular functions and interactions present in vivo. We have used this approach to examine biologic features of hepatocellular carcinoma (HCC) cells. In this study, we demonstrate that hepatocellular carcinoma (HCC) cells, fibroblasts, endothelial cells and extracellular matrix can generate organoid-like spheroids that enhanced numerous features of human HCC observed in vivo...
July 3, 2017: Organogenesis
Elena Lo Presti, Francesca Toia, Sebastiano Oieni, Simona Buccheri, Alice Turdo, Laura Rosa Mangiapane, Giuseppina Campisi, Valentina Caputo, Matilde Todaro, Giorgio Stassi, Adriana Cordova, Francesco Moschella, Gaetana Rinaldi, Serena Meraviglia, Francesco Dieli
The identification of reciprocal interactions between tumor-infiltrating immune cells and the microenviroment may help us understand mechanisms of tumor growth inhibition or progression. We have assessed the frequencies of tumor-infiltrating and circulating γδ T cells and regulatory T cells (Treg) from 47 patients with squamous cell carcinoma (SCC), to determine if they correlated with progression or survival. Vδ1 T cells infiltrated SSC tissue to a greater extent than normal skin, but SCC patients and healthy subjects had similar amounts circulating...
May 2017: Cancer Immunology Research
Xin-Gang Cui, Zhi-Tao Han, Shao-Hui He, Xing-da Wu, Tian-Rui Chen, Cheng-Hao Shao, Dan-Lei Chen, Ning Su, Yuan-Ming Chen, Ting Wang, Jing Wang, Dian-Wen Song, Wang-Jun Yan, Xing-Hai Yang, Tielong Liu, Hai-Feng Wei, Jianru Xiao
Glycolysis is a typical conduit for energy metabolism in pancreatic cancer (PC) due to the hypoxic microenviroment. Lactate dehydrogenase A (LDHA) catalyzes the conversion of pyruvate to lactate and is considered to be a key checkpoint of anaerobic glycolysis. The aim of the present study was to explore the mechanism of interactions between hypoxia, HIF-1/2α and LDHA, and the function of LDHA on PC cells by analyzing 244 PC and paratumor specimens. It was found that LDHA was over-expressed and related to tumor stages...
April 11, 2017: Oncotarget
Panagiota Stamou, Dimitra Marioli, Alexandra L Patmanidi, Argyro Sgourou, Angeliki Vittoraki, Efthymia Theofani, Chryso Pierides, Stavros Taraviras, Paul A Costeas, Alexandros Spyridonidis
BACKGROUND: Major barriers in using classical FOXP3+ regulatory T cells (Tregs) in clinical practice are their low numbers in the circulation, the lack of specific cell surface markers for efficient purification and the loss of expression of Treg signature molecules and suppressive function after in vitro expansion or in a pro-inflammatory microenviroment. A surface molecule with potent immunosuppressive function is the human leukocyte antigen-G (HLA-G), which is normally expressed in placenta protecting the "semi-allogeneic" fetus from maternal immune attack...
April 2017: Cytotherapy
Fujun Dai, Wubei Yu, Jia Song, Qian Li, Chaojie Wang, Songqiang Xie
High levels of polyamines were observed and were related to a poor prognosis in cancer patients. However, the mechanism is not obvious. The aim of this study is to mimic the extracellular polyamines in a tumor microenviroment and to explore the role of extracellular polyamines in the proliferation and migration of cancer cells. Three different concentrations of polyamines composed of putrescine, spermidine, and spermine were used. Colony formation assay, wound healing assay, and transwell migration assay were performed...
April 2017: Anti-cancer Drugs
Zhang Lingyan, Zhou Xiaoxia, Yin Weihua, Zhang Xiulian, Liu Hong, Duan Xiaopeng, Yu Cui, Luo Xiaolu, Zhong Qingfeng, Zhao Fen, Li Xianyong
89 Background: Palliative care is focused and seems as rationally anti-cancer way that have low systemic toxicity and acceptable effectiveness for stage IV cancer, especially herbal extracted medicines, which can regulate tumor microenviroment and body immune system. Our previous lab studies have indicated that TGF-beta, EGF, VEGF, IL-10 cytokines expression and mico-vessel density can be downgraded in tumor microenviroment by herbal extract preparation from Ginseng, Herba Agrimonia, Hairyvein and Arginine etc...
October 9, 2016: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
Ziwen Zhang, Detao Tao, Ping Zhang, Xue Liu, Yuchao Zhang, Jie Cheng, Hua Yuan, Laikui Liu, Hongbing Jiang
BACKGROUND: Hyaluronan synthases (HAS) control the biosynthesis of hyaluronan (HA) and critically modulate the tumor microenviroment. Cancer-associated fibroblasts (CAFs) affect the progression of a tumor by remolding the matrix. However, little is known about the role of HAS from CAFs in this process. This study aimed to determine the role of hyaluronan synthase 2 (HAS2) from CAFs in the progression of oral squamous cell carcinoma (OSCC) invasion. METHODS: HAS isoforms 1, 2, and 3 in paired sets of CAFs and normal fibroblasts (NFs) were examined by real-time PCR, and the expression of HAS2 and α-SMA in OSCC tissue sections was further evaluated using immunohistochemical staining...
November 25, 2016: Journal of Experimental & Clinical Cancer Research: CR
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