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Tumour microenvironment

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https://www.readbyqxmd.com/read/28334886/glioblastoma-associated-microglia-and-macrophages-targets-for-therapies-to-improve-prognosis
#1
Candice C Poon, Susobhan Sarkar, V Wee Yong, John J P Kelly
Glioblastoma is the most common and most malignant primary adult human brain tumour. Diagnosis of glioblastoma carries a dismal prognosis. Treatment resistance and tumour recurrence are the result of both cancer cell proliferation and their interaction with the tumour microenvironment. A large proportion of the tumour microenvironment consists of an inflammatory infiltrate predominated by microglia and macrophages, which are thought to be subverted by glioblastoma cells for tumour growth. Thus, glioblastoma-associated microglia and macrophages are logical therapeutic targets...
February 4, 2017: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/28333143/molecular-insights-of-gas6-tam-in-cancer-development-and-therapy
#2
REVIEW
Guiling Wu, Zhiqiang Ma, Wei Hu, Dongjin Wang, Bing Gong, Chongxi Fan, Shuai Jiang, Tian Li, Jianyuan Gao, Yang Yang
Since growth arrest-specific gene 6 (Gas6) was discovered in 1988, numerous studies have highlighted the role of the Gas6 protein and its receptors Tyro3, Axl and Mer (collectively referred to as TAM), in proliferation, apoptosis, efferocytosis, leukocyte migration, sequestration and platelet aggregation. Gas6 has a critical role in the development of multiple types of cancers, including pancreatic, prostate, oral, ovarian and renal cancers. Acute myelocytic leukaemia (AML) is a Gas6-dependent cancer, and Gas6 expression predicts poor prognosis in AML...
March 23, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28326574/tumour-epithelial-and-stromal-characteristics-of-hepatocellular-carcinomas-with-abundant-fibrous-stroma-fibrolamellar-versus-scirrhous-hepatocellular-carcinoma
#3
Young-Joo Kim, Hyungjin Rhee, Jeong Eun Yoo, Venancio A F Alves, Gi Jeong Kim, Hye Min Kim, Paulo Herman, Aline Chagas, Haeryoung Kim, Young Nyun Park
AIMS: The scirrhous variant of hepatocellular carcinoma (S-HCC) and fibrolamellar HCC (FL-HCC) are less common subtypes of HCC that are characterised by abundant fibrous stroma. Here, we aimed to investigate differences in the tumour microenvironment and the tumour epithelial cell characteristics of S-HCC and FL-HCC. METHODS AND RESULTS: Whole tissue sections of 17 S-HCCs and 9 FL-HCCs were subjected to immunohistochemical stains for K7, K19, EpCAM, CD56/NCAM, CD163, CD68, pSTAT3, FAP, CCN2 and Ki-67...
March 22, 2017: Histopathology
https://www.readbyqxmd.com/read/28325252/the-role-of-perineural-invasion-in-predicting-survival-in-patients-with-primary-operable-colorectal-cancer-a-systematic-review
#4
REVIEW
H C van Wyk, James Going, Paul Horgan, Donald C McMillan
Perineural invasion is a clear route for cancer cell spread however, the role of nerves in cancer progression is relatively unknown. Recent work would suggest that nerves can actively infiltrate the tumour microenvironment and stimulate cancer cell growth. Therefore, the aim of the present study was to systematically review the identification and associations of perineural invasion and survival in patients with primary operable colorectal cancer. From initial search results of 912 articles, 38 studies were selected...
April 2017: Critical Reviews in Oncology/hematology
https://www.readbyqxmd.com/read/28318643/cxcl10-alters-the-tumour-immune-microenvironment-and-disease-progression-in-a-syngeneic-murine-model-of-high-grade-serous-ovarian-cancer
#5
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...
March 16, 2017: Gynecologic Oncology
https://www.readbyqxmd.com/read/28317128/comparison-of-dce-mri-kinetic-parameters-and-fmiso-pet-uptake-parameters-in-head-and-neck-cancer-patients
#6
Urban Simoncic, Sara Leibfarth, Stefan Welz, Nina Schwenzer, Holger Schmidt, Gerald Reischl, Christina Pfannenberg, Christian la Fougère, Konstantin Nikolaou, Daniel Zips, Daniela Thorwarth
PURPOSE: Tumour hypoxia is a major cause of radiation resistance, often present in various solid tumours. Dynamic [(18) F]-fluoromisonidazole (FMISO) PET imaging is able to reliably assess tumour hypoxia. Comprehensive characterization of tumour microenvironment through FMISO-PET and dynamic contrast enhanced (DCE) MR multimodality imaging might be a valuable alternative to the dynamic FMISO-PET acquisition. The aim of this work was to explore the correlation between the FMISO-PET and DCE-MRI kinetic parameters...
March 20, 2017: Medical Physics
https://www.readbyqxmd.com/read/28301873/personalising-and-targeting-antiangiogenic-resistance-a-complex-and-multifactorial-approach
#7
REVIEW
Maria J Bueno, Silvana Mouron, Miguel Quintela-Fandino
Pathological angiogenesis involves complex and dynamic interactions between tumour cells and other lineages existing in the microenvironment of the tumour. Preclinical and clinical data suggest that tumours can show dual, different adaptive responses against antiangiogenic agents: one successful adaptation is vascular normalisation, whereas the second adaptation is elicited through vascular trimming and increased hypoxia. These phenomena depend on the type of tumour and the type of agent. The classical approach for investigating acquired resistance against antiangiogenic agents is to identify compensatory signalling pathways emerging in response to VEGF blockade, which has led to the development of highly effective drugs; however, ultimately these drugs fail...
March 16, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28288873/a-3d-model-of-tumour-angiogenic-microenvironment-to-monitor-hypoxia-effects-on-cell-interactions-and-cancer-stem-cell-selection
#8
Krzysztof Klimkiewicz, Kazimierz Weglarczyk, Guillaume Collet, Maria Paprocka, Alan Guichard, Michal Sarna, Alicja Jozkowicz, Jozef Dulak, Tadeusz Sarna, Catherine Grillon, Claudine Kieda
Tumour microenvironment determines the fate of treatments. Reconstitution of tumour conditions is mandatory for alternative in vitro methods devoted to cancer development and the selection of therapeutic strategies. This work describes a 3D model of melanoma growth in its environment. Introducing means to mimic tumour angiogenesis, which turns on tumour progression, the model shows that melanoma tumour spheroids allow reconstitution of solid tumours with stromal cells. Angiogenesis evidenced the differential recruitment of endothelial cells (EC) from early progenitors (EEPCs) to mature ECs...
March 10, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28282033/pi3k%C3%AE-and-pi3k%C3%AE-isoforms-have-distinct-functions-in-regulating-pro-tumoural-signalling-in-the-multiple-myeloma-microenvironment
#9
R E Piddock, N Loughran, C R Marlein, S D Robinson, D R Edwards, S Yu, G E Pillinger, Z Zhou, L Zaitseva, M J Auger, S A Rushworth, K M Bowles
Phosphoinositide-3-kinase and protein kinase B (PI3K-AKT) is upregulated in multiple myeloma (MM). Using a combination of short hairpin RNA (shRNA) lentivirus-mediated knockdown and pharmacologic isoform-specific inhibition we investigated the role of the PI3K p110γ (PI3Kγ) subunit in regulating MM proliferation and bone marrow microenvironment-induced MM interactions. We compared this with inhibition of the PI3K p110δ (PI3kδ) subunit and with combined PI3kδ/γ dual inhibition. We found that MM cell adhesion and migration were PI3Kγ-specific functions, with PI3kδ inhibition having no effect in MM adhesion or migration assays...
March 10, 2017: Blood Cancer Journal
https://www.readbyqxmd.com/read/28278498/hypoxia-enhances-immunosuppression-by-inhibiting-cd4-effector-t-cell-function-and-promoting-treg-activity
#10
Astrid M Westendorf, Kathrin Skibbe, Alexandra Adamczyk, Jan Buer, Robert Geffers, Wiebke Hansen, Eva Pastille, Verena Jendrossek
BACKGROUND/AIMS: Hypoxia occurs in many pathological conditions, including inflammation and cancer. Within this context, hypoxia was shown to inhibit but also to promote T cell responses. Due to this controversial function, we aimed to explore whether an insufficient anti-tumour response during colitis-associated colon cancer could be ascribed to a hypoxic microenvironment. METHODS: Colitis-associated colon cancer was induced in wildtype mice, and hypoxia as well as T cell immunity were analysed in the colonic tumour tissues...
March 8, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28276469/engineering-a-vascularised-3d-in-vitro-model-of-cancer-progression
#11
Tarig Magdeldin, Víctor López-Dávila, Judith Pape, Grant W W Cameron, Mark Emberton, Marilena Loizidou, Umber Cheema
The hallmark of tumours is the ability of cancerous cells to promote vascular growth, to disseminate and invade to distant organs. The metastatic process is heavily influenced by the extracellular matrix (ECM) density and composition of the surrounding tumour microenvironment. These microenvironmental cues, which include hypoxia, also regulate the angiogenic processes within a tumour, facilitating the spread of cancer cells. We engineered compartmentalized biomimetic colorectal tumouroids with stromal surrounds that comprised a range of ECM densities, composition and stromal cell populations...
March 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28276425/the-shc1-adaptor-simultaneously-balances-stat1-and-stat3-activity-to-promote-breast-cancer-immune-suppression
#12
Ryuhjin Ahn, Valérie Sabourin, Alicia M Bolt, Steven Hébert, Stephanie Totten, Nicolas De Jay, Maria Carolina Festa, Yoon Kow Young, Young Kyuen Im, Tony Pawson, Antonis E Koromilas, William J Muller, Koren K Mann, Claudia L Kleinman, Josie Ursini-Siegel
Tyrosine kinase signalling within cancer cells is central to the establishment of an immunosuppressive microenvironment. Although tyrosine kinase inhibitors act, in part, to augment adaptive immunity, the increased heterogeneity and functional redundancy of the tyrosine kinome is a hurdle to achieving durable responses to immunotherapies. We previously identified the Shc1 (ShcA) scaffold, a central regulator of tyrosine kinase signalling, as essential for promoting breast cancer immune suppression. Herein we show that the ShcA pathway simultaneously activates STAT3 immunosuppressive signals and impairs STAT1-driven immune surveillance in breast cancer cells...
March 9, 2017: Nature Communications
https://www.readbyqxmd.com/read/28275910/mechanisms-of-drug-resistance-in-melanoma
#13
Matthew Winder, Amaya Virós
Metastatic melanoma is associated with poor outcome and is largely refractory to the historic standard of care. In recent years, the development of targeted small-molecule inhibitors and immunotherapy has revolutionised the care and improved the overall survival of these patients. Therapies targeting BRAF and MEK to block the mitogen-activated protein kinase (MAPK) pathway were the first to show unprecedented clinical responses. Following these encouraging results, antibodies targeting immune checkpoint inhibition molecules cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), programmed cell death (PD)-1, and PD-ligand1(PD-L1) demonstrated sustained tumour regression in a significant subset of patients by enabling an anti-tumour immunologic response...
March 9, 2017: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/28275390/dual-role-of-inflammatory-mediators-in-cancer
#14
REVIEW
T G Shrihari
Inflammation is the body's response to noxious stimuli such as infectious, physiological or chemical agents, it releases various inflammatory mediators via immune cells such as neutrophils, macrophages, and lymphocytes. These inflammatory mediators are growth factors, chemokines, and cytokines. Reactive oxygen species (ROS) and nitrogen species (RNS) activate transcriptional factors (NF-KB, STAT-3) and bring about cellular proliferation, genomic instability, angiogenesis, resistance to apoptosis, invasion, and metastasis...
2017: Ecancermedicalscience
https://www.readbyqxmd.com/read/28274999/tumour-activated-neutrophils-in-gastric-cancer-foster-immune-suppression-and-disease-progression-through-gm-csf-pd-l1-pathway
#15
Ting-Ting Wang, Yong-Liang Zhao, Liu-Sheng Peng, Na Chen, Weisan Chen, Yi-Pin Lv, Fang-Yuan Mao, Jin-Yu Zhang, Ping Cheng, Yong-Sheng Teng, Xiao-Long Fu, Pei-Wu Yu, Gang Guo, Ping Luo, Yuan Zhuang, Quan-Ming Zou
OBJECTIVE: Neutrophils are prominent components of solid tumours and exhibit distinct phenotypes in different tumour microenvironments. However, the nature, regulation, function and clinical relevance of neutrophils in human gastric cancer (GC) are presently unknown. DESIGN: Flow cytometry analyses were performed to examine levels and phenotype of neutrophils in samples from 105 patients with GC. Kaplan-Meier plots for overall survival were performed using the log-rank test...
March 8, 2017: Gut
https://www.readbyqxmd.com/read/28273064/class-iia-hdac-inhibition-reduces-breast-tumours-and-metastases-through-anti-tumour-macrophages
#16
Jennifer L Guerriero, Alaba Sotayo, Holly E Ponichtera, Jessica A Castrillon, Alexandra L Pourzia, Sara Schad, Shawn F Johnson, Ruben D Carrasco, Suzan Lazo, Roderick T Bronson, Scott P Davis, Mercedes Lobera, Michael A Nolan, Anthony Letai
Although the main focus of immuno-oncology has been manipulating the adaptive immune system, harnessing both the innate and adaptive arms of the immune system might produce superior tumour reduction and elimination. Tumour-associated macrophages often have net pro-tumour effects, but their embedded location and their untapped potential provide impetus to discover strategies to turn them against tumours. Strategies that deplete (anti-CSF-1 antibodies and CSF-1R inhibition) or stimulate (agonistic anti-CD40 or inhibitory anti-CD47 antibodies) tumour-associated macrophages have had some success...
March 8, 2017: Nature
https://www.readbyqxmd.com/read/28262747/smad3-promotes-cancer-progression-by-inhibiting-e4bp4-mediated-nk-cell-development
#17
Patrick Ming-Kuen Tang, Shuang Zhou, Xiao-Ming Meng, Qing-Ming Wang, Chun-Jie Li, Guang-Yu Lian, Xiao-Ru Huang, Yong-Jiang Tang, Xin-Yuan Guan, Bryan Ping-Yen Yan, Ka-Fai To, Hui-Yao Lan
TGF-β is known to influence tumour progression. Here we report an additional role of Smad3 in the tumour microenvironment regulating cancer progression. Deletion or inhibition of Smad3 in the tumour microenvironment suppresses tumour growth, invasion and metastasis in two syngeneic mouse tumour models. Smad3(-/-) bone marrow gives rise to an expanded NK cell population with enhanced tumour-suppressive activities in vivo, and promotes differentiation of NK cells ex vivo. We identify E4BP4/NFIL3 as a direct Smad3 target gene critical for NK cell differentiation...
March 6, 2017: Nature Communications
https://www.readbyqxmd.com/read/28260049/inflammatory-peroxidases-promote-breast-cancer-progression-in-mice-via-regulation-of-the-tumour-microenvironment
#18
Vasilios Panagopoulos, Damien A Leach, Irene Zinonos, Vladimir Ponomarev, Giovanni Licari, Vasilios Liapis, Wendy V Ingman, Peter Anderson, Mark O DeNichilo, Andreas Evdokiou
Myeloperoxidase (MPO) and eosinophil peroxidase (EPO) are heme-containing enzymes, well known for their antimicrobial activity, are released in high quantities by infiltrating immune cells in breast cancer. However, the functional importance of their presence within the tumour microenvironment is unclear. We have recently described a new role for peroxidases as key regulators of fibroblast and endothelial cell functionality. In the present study, we investigate for the first time, the ability of peroxidases to promote breast cancer development and progression...
February 20, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28255366/liposomal-nanoparticles-carrying-anti-il6r-antibody-to-the-tumour-microenvironment-inhibit-metastasis-in-two-molecular-subtypes-of-breast-cancer-mouse-models
#19
Chunlei Guo, Yanan Chen, Wenjuan Gao, Antao Chang, Yujie Ye, Wenzhi Shen, Yunping Luo, Shengyong Yang, Peiqing Sun, Rong Xiang, Na Li
Tumour microenvironment (TME) contributes significantly towards potentiating the stemness and metastasis properties of cancer cells. IL6-Stat3 is one of the important cell signaling pathways in mediating the communication between tumour and immune cells. Here, we have systematically developed a novel anti-CD44 antibody-mediated liposomal nanoparticle delivery system loaded with anti-IL6R antibody, which could specifically target the TME of CD44(+) breast cancer cells in different mouse models for triple negative and luminal breast cancer...
2017: Theranostics
https://www.readbyqxmd.com/read/28250926/tumour-cell-conditioned-medium-reveals-greater-m2-skewing-of-macrophages-in-the-absence-of-properdin
#20
Izzat A M Al-Rayahi, Michael J Browning, Cordula Stover
INTRODUCTION: The tumour microenvironment is shaped by the interaction of immune, non immune, and tumour cells present in close proximity. Tumour cells direct the development of a locally immune suppressed state, affecting the activity of anti tumour T cells and preparing the escape phase of tumour development. Macrophages in the tumour typically develop into so-called tumour associated macrophages with a distinct profile of activities which lead to a reduction in inflammation and antigen presentation...
March 2017: Immunity, Inflammation and Disease
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