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Tumour microenvironment

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https://www.readbyqxmd.com/read/28921585/allergooncology-opposite-outcomes-of-immune-tolerance-in-allergy-and-cancer
#1
E Jensen-Jarolim, H J Bax, R Bianchini, S Crescioli, T R Daniels-Wells, D Dombrowicz, E Fiebiger, H J Gould, S Irshad, J Janda, D H Josephs, F Levi-Schaffer, L O Mahony, G Pellizzari, M L Penichet, F Redegeld, F Roth-Walter, J Singer, E Untersmayr, L Vangelista, S N Karagiannis
While desired for the cure of allergy, regulatory immune cell subsets and non-classical Th2-biased inflammatory mediators in the tumour microenvironment can contribute to immune suppression and escape of tumours from immunological detection and clearance. A key aim in the cancer field is therefore to design interventions that can break immunological tolerance and halt cancer progression, whereas on the contrary allergen immunotherapy exactly aims to induce tolerance. In this position paper, we review insights on immune tolerance derived from allergy and from cancer inflammation, focusing on what is known about the roles of key immune cells and mediators...
September 16, 2017: Allergy
https://www.readbyqxmd.com/read/28920955/mir-25-93-mediates-hypoxia-induced-immunosuppression-by-repressing-cgas
#2
Min-Zu Wu, Wei-Chung Cheng, Su-Feng Chen, Shin Nieh, Carolyn O'Connor, Chia-Lin Liu, Wen-Wei Tsai, Cheng-Jang Wu, Lorena Martin, Yaoh-Shiang Lin, Kou-Juey Wu, Li-Fan Lu, Juan Carlos Izpisua Belmonte
The mechanisms by which hypoxic tumours evade immunological pressure and anti-tumour immunity remain elusive. Here, we report that two hypoxia-responsive microRNAs, miR-25 and miR-93, are important for establishing an immunosuppressive tumour microenvironment by downregulating expression of the DNA sensor cGAS. Mechanistically, miR-25/93 targets NCOA3, an epigenetic factor that maintains basal levels of cGAS expression, leading to repression of cGAS during hypoxia. This allows hypoxic tumour cells to escape immunological responses induced by damage-associated molecular pattern molecules, specifically the release of mitochondrial DNA...
September 18, 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/28920587/complement-in-cancer-untangling-an-intricate-relationship
#3
REVIEW
Edimara S Reis, Dimitrios C Mastellos, Daniel Ricklin, Alberto Mantovani, John D Lambris
In tumour immunology, complement has traditionally been considered as an adjunctive component that enhances the cytolytic effects of antibody-based immunotherapies, such as rituximab. Remarkably, research in the past decade has uncovered novel molecular mechanisms linking imbalanced complement activation in the tumour microenvironment with inflammation and suppression of antitumour immune responses. These findings have prompted new interest in manipulating the complement system for cancer therapy. This Review summarizes our current understanding of complement-mediated effector functions in the tumour microenvironment, focusing on how complement activation can act as a negative or positive regulator of tumorigenesis...
September 18, 2017: Nature Reviews. Immunology
https://www.readbyqxmd.com/read/28913366/the-differential-contribution-of-the-innate-immune-system-to-a-good-pathological-response-in-the-breast-and-axillary-lymph-nodes-induced-by-neoadjuvant-chemotherapy-in-women-with-large-and-locally-advanced-breast-cancers
#4
Viriya Kaewkangsadan, Chandan Verma, Jennifer M Eremin, Gerard Cowley, Mohammad Ilyas, Sukchai Satthaporn, Oleg Eremin
The tumour microenvironment consists of malignant cells, stroma, and immune cells. The role of adaptive immunity in inducing a pathological complete response (pCR) in breast cancer with neoadjuvant chemotherapy (NAC) is well studied. The contribution of innate immunity, however, is poorly documented. Breast tumours and axillary lymph nodes (ALNs) from 33 women with large and locally advanced breast cancers (LLABCs) undergoing NAC were immunohistochemically assessed for tumour-infiltrating macrophages (TIMs: M1 and M2), neutrophils (TINs), and dendritic cells (TIDCs) using labelled antibodies and semiquantitative methods...
2017: Journal of Immunology Research
https://www.readbyqxmd.com/read/28912578/tumour-acidosis-from-the-passenger-to-the-driver-s-seat
#5
REVIEW
Cyril Corbet, Olivier Feron
The high metabolic demand of cancer cells leads to an accumulation of H(+) ions in the tumour microenvironment. The disorganized tumour vasculature prevents an efficient wash-out of H(+) ions released into the extracellular medium but also favours the development of tumour hypoxic regions associated with a shift towards glycolytic metabolism. Under hypoxia, the final balance of glycolysis, including breakdown of generated ATP, is the production of lactate and a stoichiometric amount of H(+) ions. Another major source of H(+) ions results from hydration of CO2 produced in the more oxidative tumour areas...
September 15, 2017: Nature Reviews. Cancer
https://www.readbyqxmd.com/read/28912577/classifying-the-evolutionary-and-ecological-features-of-neoplasms
#6
REVIEW
Carlo C Maley, Athena Aktipis, Trevor A Graham, Andrea Sottoriva, Amy M Boddy, Michalina Janiszewska, Ariosto S Silva, Marco Gerlinger, Yinyin Yuan, Kenneth J Pienta, Karen S Anderson, Robert Gatenby, Charles Swanton, David Posada, Chung-I Wu, Joshua D Schiffman, E Shelley Hwang, Kornelia Polyak, Alexander R A Anderson, Joel S Brown, Mel Greaves, Darryl Shibata
Neoplasms change over time through a process of cell-level evolution, driven by genetic and epigenetic alterations. However, the ecology of the microenvironment of a neoplastic cell determines which changes provide adaptive benefits. There is widespread recognition of the importance of these evolutionary and ecological processes in cancer, but to date, no system has been proposed for drawing clinically relevant distinctions between how different tumours are evolving. On the basis of a consensus conference of experts in the fields of cancer evolution and cancer ecology, we propose a framework for classifying tumours that is based on four relevant components...
September 15, 2017: Nature Reviews. Cancer
https://www.readbyqxmd.com/read/28912377/immune-response-in-the-thyroid-cancer-microenvironment-making-immunotherapy-a-possible-mission
#7
Robert C Mould, Jacob P van Vloten, Amanda W K AuYeung, Khalil Karimi, Byram W Bridle
The incidence of thyroid cancers has been steadily increasing worldwide over the past few decades. Although five-year survival rates for differentiated thyroid cancers are upwards of 90%, clinical outcomes for patients with undifferentiated, recurrent and/or metastatic disease are often dismal despite conventional interventions. As such, there is a demand for novel treatment options. Cancer immunotherapy represents the ultimate form of personalized medicine by leveraging the specificity and potency of a patient's immune system to kill their tumour...
September 14, 2017: Endocrine-related Cancer
https://www.readbyqxmd.com/read/28903185/mixed-micelles-for-encapsulation-of-doxorubicin-with-enhanced-in-vitro-cytotoxicity-on-breast-and-ovarian-cancer-cell-lines-versus-doxil-%C3%A2
#8
Maximiliano Cagel, Ezequiel Bernabeu, Lorena Gonzalez, Eduardo Lagomarsino, Marcela Zubillaga, Marcela A Moretton, Diego A Chiappetta
Doxorubicin (DOX) is used as a "first-line" antineoplastic drug in ovarian and metastatic breast cancer. However, serious side effects, such as cardiotoxicity have been reported after DOX intravenous administration. Hence, we investigated different micelle-former biomaterials, as Soluplus(®), Pluronic F127, Tetronic T1107 and d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) to develop a potential mixed micellar nanocarrier for DOX delivery. Since DOX hydrochloride is a poor candidate to be encapsulated inside the hydrophobic core of the mixed micelles, we assayed a hydrophobic complex between DOX and sodium deoxycholate (NaDC) as an excellent candidate to be encapsulated within polymeric micelles...
September 9, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28900472/predictive-and-prognostic-impact-of-tumour-infiltrating-lymphocytes-in-triple-negative-breast-cancer-treated-with-neoadjuvant-chemotherapy
#9
Carmen Herrero-Vicent, Angel Guerrero, Joaquin Gavilá, Francisco Gozalbo, Abraham Hernández, Sergio Sandiego, Maria Asunción Algarra, Ana Calatrava, Vicente Guillem-Porta, Amparo Ruiz-Simón
INTRODUCTION: In locally and locally advanced triple-negative breast cancer (TNBC), neoadjuvant chemotherapy (NAC) only induces a pCR in 30-35% of patients. Clinical and pathological factors are not enough to distinguish the patients who have no chance of a pCR or not. The tumour microenvironment is critical for cancer and tumour-infiltrating lymphocytes (TIL). Moreover, the NAC scenario is the perfect setting to study possible changes in TIL levels. MATERIAL AND METHODS: Using our prospective maintained breast cancer (BC) database, we identified 164 TNBC patients treated with NAC between 1998 and 2015 with enough samples of diagnostic biopsy and after surgery...
2017: Ecancermedicalscience
https://www.readbyqxmd.com/read/28895566/wnt-signalling-in-prostate-cancer
#10
REVIEW
Virginia Murillo-Garzón, Robert Kypta
Genome sequencing and gene expression analyses of prostate tumours have highlighted the potential importance of genetic and epigenetic changes observed in WNT signalling pathway components in prostate tumours - particularly in the development of castration-resistant prostate cancer. WNT signalling is also important in the prostate tumour microenvironment, in which WNT proteins secreted by the tumour stroma promote resistance to therapy, and in prostate cancer stem or progenitor cells, in which WNT-β-catenin signals promote self-renewal or expansion...
September 12, 2017: Nature Reviews. Urology
https://www.readbyqxmd.com/read/28892775/challenges-and-perspectives-in-the-immunotherapy-of-hodgkin-lymphoma
#11
REVIEW
Jean-Marie Michot, Julien Lazarovici, David Ghez, Alina Danu, Christophe Fermé, Amélie Bigorgne, Vincent Ribrag, Aurélien Marabelle, Sandrine Aspeslagh
Hodgkin lymphoma (HL) was one of the first few cancers to be cured first with radiotherapy alone and then with a combination of chemotherapy and radiotherapy. Around 80% of the patients with HL will be cured by first-line therapy. However, the ionising radiation not only produces cytotoxicity but also induces alterations in the microenvironment, and patients often struggle with the long-term consequences of these treatments, such as cardiovascular disorders, lung diseases and secondary malignancies. Hence, it is essential to improve treatments while avoiding delayed side-effects...
September 8, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28891394/the-role-of-chemokines-in-thyroid-carcinoma
#12
Sharinie Yapa, Omar Mulla, Victoria Green, James England, John Greenman
Global incidence of thyroid cancer is increasing and metastatic spread to lymph nodes is common in papillary thyroid carcinoma. The metastatic course of thyroid carcinoma is an intricate process involving invasion, angiogenesis, cell trafficking, extravasation, organ specific homing and growth. A key aspect in this process involves a multitude of interactions between chemokines and their receptors. Chemokines are a group of small proteins, which act to elicit normal physiological and immune responses principally through recruitment of specific cell populations to site of infection or malignancy...
September 11, 2017: Thyroid: Official Journal of the American Thyroid Association
https://www.readbyqxmd.com/read/28888113/tissue-engineered-human-3d-model-of-bladder-cancer-for-invasion-study-and-drug-discovery
#13
Cassandra Ringuette Goulet, Geneviève Bernard, Stéphane Chabaud, Amélie Couture, Alexandre Langlois, Bertrand Neveu, Frédéric Pouliot, Stéphane Bolduc
The tumour microenvironment is critical to both the initiation and maintenance of tumorigenesis. Reconstitution of the microenvironment is a major challenge for in vitro cancer models. Indeed, conventional 2D culture systems cannot replicate the complexity, diversity and dynamic nature of the tumour microenvironment. In this study, we have developed a 3D endotheliazed vesical equivalent by using tissue engineering from primary human cells in which non-invasive or invasive bladder cancer (BCa) cell lines, cultured as compact spheroids, were incorporated...
August 29, 2017: Biomaterials
https://www.readbyqxmd.com/read/28888050/significance-of-perivascular-tumour-cells-defined-by-cd109-expression-in-progression-of-glioma
#14
Yukihiro Shiraki, Shinji Mii, Atsushi Enomoto, Hiroyuki Momota, Yi-Peng Han, Takuya Kato, Kaori Ushida, Akira Kato, Naoya Asai, Yoshiki Murakumo, Kosuke Aoki, Hiromichi Suzuki, Fumiharu Ohka, Toshihiko Wakabayashi, Tomoki Todo, Seishi Ogawa, Atsushi Natsume, Masahide Takahashi
In the progression of glioma, tumour cells often exploit the perivascular microenvironment to promote their survival and resistance to conventional therapies. Some of these cells are considered to be brain tumour stem cells (BTSCs); however, the molecular nature of perivascular tumour cells has not been specifically clarified because of the complexity of glioma. Here, we identified CD109, a glycosylphosphatidylinositol- anchored protein and regulator of multiple signalling pathways, as a critical regulator of the progression of lower-grade glioma (World Health Organization grade II/III) by clinicopathological and whole genome sequencing analysis of tissues from human glioma...
September 9, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/28887504/macrophages-unlock-progression-of-breast-cancer-cells-experiencing-matrigel-segregation-in-transplantation-models
#15
Misa Ogura, Victoria L Bridgeman, Ilaria Malanchi
Basement membrane matrix proteins, such as matrigel, are able to improve the efficiency of tumour transplantation. This assay represents the gold standard to measure tumour initiation potential in vivo of a limited number of cancer cells. However, in culture conditions, matrigel directly signals to cancer cells altering their phenotype. We here investigate how matrigel influences the tumour reconstitution dynamics of breast cancer cells in vivo. This is particularly relevant in the setting of limiting dilution assay where cells are transplanted in a relatively high amount of Matrigel...
September 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28885562/human-cd3-t-cells-with-the-anti-erbb2-chimeric-antigen-receptor-exhibit-efficient-targeting-and-induce-apoptosis-in-erbb2-overexpressing-breast-cancer-cells
#16
Rusheni Munisvaradass, Suresh Kumar, Chandramohan Govindasamy, Khalid S Alnumair, Pooi Ling Mok
Breast cancer is a common malignancy among women. The innate and adaptive immune responses failed to be activated owing to immune modulation in the tumour microenvironment. Decades of scientific study links the overexpression of human epidermal growth factor receptor 2 (ERBB2) antigen with aggressive tumours. The Chimeric Antigen Receptor (CAR) coding for specific tumour-associated antigens could initiate intrinsic T-cell signalling, inducing T-cell activation, and cytotoxic activity without the need for major histocompatibility complex recognition...
September 8, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28878809/are-online-prediction-tools-a-valid-alternative-to-genomic-profiling-in-the-context-of-systemic-treatment-of-er-positive-breast-cancer
#17
REVIEW
Umar Wazir, Kinan Mokbel, Amtul Carmichael, Kefah Mokbel
BACKGROUND: Clinicians use clinical and pathological parameters, such as tumour size, grade and nodal status, to make decisions on adjuvant treatments for breast cancer. However, therapeutic decisions based on these features tend to vary due to their subjectivity. Computational and mathematical algorithms were developed using clinical outcome data from breast cancer registries, such as Adjuvant! Online and NHS PREDICT. More recently, assessments of molecular profiles have been applied in the development of better prognostic tools...
2017: Cellular & Molecular Biology Letters
https://www.readbyqxmd.com/read/28877959/prognostic-role-of-tumour-associated-macrophages-and-regulatory-t-cells-in-ebv-positive-and-ebv-negative-nasopharyngeal-carcinoma
#18
Marc L Ooft, Jolique A van Ipenburg, Maxime E Sanders, Mariette Kranendonk, Ingrid Hofland, Remco de Bree, Senada Koljenović, Stefan M Willems
AIMS: Tumour-associated macrophages (TAMs) and regulatory T cells (Tregs) form a special niche supporting tumour progression, and both correlate with worse survival in head and neck cancers. However, the prognostic role of TAM and Tregs in nasopharyngeal carcinoma (NPC) is still unknown. Therefore, we determined differences in TAMs and Tregs in different NPC subtypes, and their prognostic significance. METHODS: Tissue of 91 NPCs was assessed for TAMs and Tregs by determination of CD68, CD163, CD206 and FOXP3 expression in the tumour microenvironment...
September 6, 2017: Journal of Clinical Pathology
https://www.readbyqxmd.com/read/28875845/new-trends-in-anti-cancer-therapy-combining-conventional-chemotherapeutics-with-novel-immunomodulators
#19
Amy L Wilson, Magdalena Plebanski, Andrew N Stephens
Cancer is one of the leading causes of death worldwide, and current research has focused on the discovery of novel approaches to effectively treat this disease. Recently, a considerable number of clinical trials have demonstrated the success of immunomodulatory therapies for the treatment of cancer. Monoclonal antibodies can target components of the immune system to either i) agonise co-stimulatory molecules, such as CD137, OX40 and CD40; or ii) inhibit immune checkpoints, such as cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), programmed cell death-1 (PD-1) and its corresponding ligand PD-L1...
August 29, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28874690/a-single-neonatal-administration-of-bisphenol-a-induces-higher-tumour-weight-associated-to-changes-in-tumour-microenvironment-in-the-adulthood
#20
Margarita Isabel Palacios-Arreola, Karen Elizabeth Nava-Castro, Víctor Hugo Del Río-Araiza, Nashla Yazmín Pérez-Sánchez, Jorge Morales-Montor
BPA is an oestrogenic endocrine disrupting chemical compound. Exposure to BPA in as early as pregnancy leads to lifelong effects. Since endocrine and immune systems interact in a bidirectional manner, endocrine disruption may cause permanent alterations of the immune system, affecting a future anti-tumoral response. Neonate (PND 3) female syngeneic BALB/c mice were exposed to a single dose of 250 µg/kg BPA. Once sexual maturity was reached, a mammary tumour was induced injecting 4T1 cells in situ, these cells are derived from a spontaneous adenocarcinoma in a BALB/c mouse and therefore allows for an immunocompetent recipient...
September 5, 2017: Scientific Reports
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