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Cancer AND Immunology

Pankaj Garg
A new modality of targeting therapeutic drugs based on the use of bacteriophage (virus), as an emerging tool for specific targeting and for vaccine development, has been an area of interest for genetic and cancer research. The approach is based on genetic manipulation and modification in the chemical structure of a filamentous bacteriophage that facilitates its application not only for in vivo imaging but also for therapeutic purpose, as a gene delivery vehicle, as drug carriers, and also as an immunomodulatory agent...
March 2019: Journal of Cancer Research and Therapeutics
Giovanni Manzo
Here, I propose that cancer stem cells (CSCs) would be equivalent to para-embryonic stem cells (p-ESCs), derived from adult cells de-re-programmed to a ground state. p-ESCs would differ from ESCs by the absence of genomic homeostasis. A p-ESC would constitute the cancer cell of origin (i-CSC or CSC0), capable of generating an initial tumor, corresponding to a pre-implantation blastocyst. In a niche with proper signals, it would engraft as a primary tumor, corresponding to a post-implantation blastocyst. i-CSC progeny would form primary pluripotent and slow self-renewing CSCs (CSC1s), blocked in an undifferentiated state, corresponding to epiblast cells; CSC1s would be tumor-initiating cells (TICs)...
2019: Frontiers in Cell and Developmental Biology
Mervin B Agyeman, Verna D Vanderpuye, Joel Yarney
Local tumor control and symptom relief have been the major advantage of radiotherapy in clinical practice. In the past years, the systemic anti-tumor effect of radiotherapy, also known as the abscopal effect, has been reported with limited studies. With the advent of immunotherapy, the frequency of the abscopal effect has increased in patients who receive sequential treatment with radiotherapy and immunotherapy or patients who receive radiotherapy after acquiring resistance to immunotherapy. A novel cancer treatment modality, such as molecular targeted therapy, has been associated with the immune response within the tumor but its systemic anti-tumor effect, when combined with radiotherapy, is yet to be documented...
January 8, 2019: Curēus
Yu Fujita, Roberto Tinoco, Yan Li, Daniela Senft, Ze'ev A Ronai
Considerable progress has been made in understanding the contribution of E3 ubiquitin ligases to health and disease, including the pathogenesis of immunological disorders. Ubiquitin ligases exert exquisite spatial and temporal control over protein stability and function, and are thus crucial for the regulation of both innate and adaptive immunity. Given that immune responses can be both detrimental (autoimmunity) and beneficial (antitumor immunity), it is vital to understand how ubiquitin ligases maintain immunological homeostasis...
March 18, 2019: Trends in Molecular Medicine
Denise Lau, Alexandria M Bobe, Aly A Khan
RNA sequencing (RNA-seq) provides an efficient high-throughput technique to robustly characterize the tumor immune microenvironment (TME). The increasing use of RNA-seq in clinical and basic science settings provides a powerful opportunity to access novel therapeutic biomarkers in the TME. Advanced computational methods are making it possible to resolve the composition of the tumor immune infiltrate, infer the immunological phenotypes of those cells, and assess the immune receptor repertoire in RNA-seq data...
March 2019: Trends in Cancer
Akiko Takikawa, Isao Usui, Shiho Fujisaka, Koichi Tsuneyama, Keisuke Okabe, Takashi Nakagawa, Allah Nawaz, Tomonobu Kado, Teruo Jojima, Yoshimasa Aso, Yoshihiro Hayakawa, Kunikimi Yagi, Kazuyuki Tobe
AIMS/INTRODUCTION: Chronic inflammation of the liver is often observed with obesity or type 2 diabetes. In these pathological conditions, the immunological cells, such as macrophages, play important roles in the development or growth of the liver cancer. Recently, it was reported that HIF-1α is a key molecule for the acquisition of inflammatory M1 polarity of macrophages. In the present study, we examined the effects of altered macrophage polarity on obesity and diabetes-associated liver cancer using macrophage-specific HIF-1α knockout (KO) mice...
March 21, 2019: Journal of Diabetes Investigation
Axel Ducret, Ian James, Sabine Wilson, Martina Feilke, Andreas Tebbe, Nikolaj Dybowski, Sarah Elschenbroich, Martin Klammer, Adele Blackler, Wei-Li Liao, Yuan Tian, Thomas Friess, Birgit Bossenmaier, Gabriele Dietmann, Christoph Schaab, Todd Hembrough, Maurizio Ceppi
Human protein biomarker discovery relies heavily on pre-clinical models, in particular established cell lines and patient-derived xenografts, but confirmation studies in primary tissue are essential to demonstrate clinical relevance. We describe in this study the process that was followed to clinically translate a 5-protein response signature predictive for the activity of an anti-HER3 monoclonal antibody (lumretuzumab) originally measured in fresh frozen xenograft tissue. We detail the development, qualification, and validation of the multiplexed targeted mass spectrometry assay used to assess the signature performance in formalin-fixed, paraffin-embedded human clinical samples collected in a phase Ib trial designed to evaluate lumretuzumab in patients with metastatic breast cancer...
2019: PloS One
Mark Yarchoan, Lee A Albacker, Alexander C Hopkins, Meagan Montesion, Karthikeyan Murugesan, Teena T Vithayathil, Neeha Zaidi, Nilofer S Azad, Daniel A Laheru, Garrett M Frampton, Elizabeth M Jaffee
BACKGROUND: PD-L1 expression and tumor mutational burden (TMB) have emerged as important biomarkers of response to immune checkpoint inhibitor (ICI) therapy. These biomarkers have each succeeded and failed in predicting responders for different cancer types. We sought to describe the PD-L1 expression landscape across the spectrum of ICI-responsive human cancers, and to determine the relationship between PD-L1 expression, TMB, and response rates to ICIs. METHODS: We assessed 9887 clinical samples for PD-L1 expression and TMB...
March 21, 2019: JCI Insight
Fatima Ahmetlić, Tanja Riedel, Nadine Hömberg, Vera Bauer, Nico Trautwein, Albert Geishauser, Tim Sparwasser, Stefan Stevanović, Martin Röcken, Ralph Mocikat
Foxp3+ regulatory T cells (Tregs) sustain immune homeostasis and may contribute to immune escape in malignant disease. As a prerequisite for developing immunologic approaches in cancer therapy, it is necessary to understand the ontogeny and the antigenic specificities of tumor-infiltrating Tregs. We addressed this question by using a λ-MYC transgenic mouse model of endogenously arising B-cell lymphoma, which mirrors key features of human Burkitt lymphoma. We show that Foxp3+ Tregs suppress antitumor responses in endogenous lymphoma...
March 20, 2019: Cancer Immunology Research
Jairo Moyano, Luisa Aguirre
Opioids interact with both innate and adaptive immune systems and have direct effects on opioid receptors located on immune cells. Research on this topic has provided evidence of the opioid influence on the immune response associated with surgical stress. The immunological effects of opioids are currently being investigated, particularly whether they influence the outcome of surgery or the underlying disease regarding important aspects like infection or cancer progression. This review addresses background research related to the influence of the opioid receptor on the immune system, the immunosuppressive effect associated with major opioids during the perioperative period, and their clinical relevance...
February 2019: Revista da Associação Médica Brasileira
Marcus A Alvarez, Júlia Pedó Freitas, S Mazher Hussain, Evan S Glazer
BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancerrelated mortality in the USA, and the overall incidence of the disease is increasing such that it is expected to be the third leading cause of cancer-related deaths in the next decade. Minimal improvements in therapy have not changed the overall mortality rate over the past decade for patients with PDAC. The purpose of this review is to identify new data regardign the role of Transforming growth factor beta (TGF-β) based therapeuics in patients with PDAC...
March 20, 2019: Journal of Gastrointestinal Cancer
Dante Alexander Patrick Louie, Shan Liao
Lymphatic vessels collect and transport lymph and pathogens to the draining lymph node (LN) to generate proper immune protection. A layer of macrophages that strategically line the LN subcapsular sinus (SCS) is directly exposed to the afferent lymph and are denoted as SCS macrophages. These macrophages are the frontline of immune defense that interact with lymph-borne antigens. The importance of these macrophages in limiting the spread of pathogens has been demonstrated in both viral and bacterial infection...
2019: Frontiers in Immunology
Natalia M Tijaro-Ovalle, Theodoros Karantanos, Hong-Tao Wang, Vassiliki A Boussiotis
Utilization of the adaptive immune system against malignancies, both by immune-based therapies to activate T cells in vivo to attack cancer and by T-cell therapies to transfer effector cytolytic T lymphocytes (CTL) to the cancer patient, represent major novel therapeutic advancements in oncologic therapy. Allogeneic hematopoietic stem cell (HSC) transplantation (HSCT) is a form of cell-based therapy, which replaces the HSC in the patient's bone marrow but also serves as a T-cell therapy due to the Graft-vs...
2019: Frontiers in Immunology
Aleksandra Altobelli, Michael Bauer, Karelia Velez, Timothy L Cover, Anne Müller
The gastric bacterium Helicobacter pylori causes a persistent infection that is directly responsible for gastric ulcers and gastric cancer in some patients and protective against allergic and other immunological disorders in others. The two outcomes of the Helicobacter -host interaction can be modeled in mice that are infected as immunocompetent adults and as neonates, respectively. Here, we have investigated the contribution of the Helicobacter immunomodulator VacA to H. pylori -specific local and systemic immune responses in both models...
March 19, 2019: MBio
Chiara Napoletano, Ilary Ruscito, Filippo Bellati, Ilaria Grazia Zizzari, Hassan Rahimi, Maria Luisa Gasparri, Morena Antonilli, Pierluigi Benedetti Panici, Aurelia Rughetti, Marianna Nuti
Increasing evidence strongly suggests that bevacizumab compound impacts the immunological signature of cancer patients and normalizes tumor vasculature. This study aims to investigate the correlation between the clinical response to bevacizumab-based chemotherapy and the improvement of immune fitness of multi-treated ovarian cancer patients. Peripheral blood mononuclear cells (PBMCs) of 20 consecutive recurrent ovarian cancer patients retrospectively selected to have received bevacizumab or non-bevacizumab-based chemotherapy (Bev group and Ctrl group, respectively) were analyzed...
March 18, 2019: Journal of Clinical Medicine
Jan Philipp Bewersdorf, Maximilian Stahl, Amer M Zeidan
Immune system evasion is essential for tumor cell survival and is mediated by the immunosuppressive tumor microenvironment and the activation of inhibitory immune checkpoints. While immune checkpoint-based therapy yielded impressive results in several advanced solid malignancies such as melanoma and non-small cell lung cancer, its role in acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) is still evolving. Areas covered: Here we review the immunology in the tumor microenvironment in the bone marrow and discuss the current preclinical and clinical data for immune checkpoint-based therapy in myeloid neoplasms...
March 19, 2019: Expert Review of Anticancer Therapy
Amin Aalipour, Hui-Yen Chuang, Surya Murty, Aloma L D'Souza, Seung-Min Park, Gunsagar S Gulati, Chirag B Patel, Corinne Beinat, Federico Simonetta, Ivana Martinić, Gayatri Gowrishankar, Elise R Robinson, Eamon Aalipour, Zahra Zhian, Sanjiv S Gambhir
Endogenous biomarkers remain at the forefront of early disease detection efforts, but many lack the sensitivities and specificities necessary to influence disease management. Here, we describe a cell-based in vivo sensor for highly sensitive early cancer detection. We engineer macrophages to produce a synthetic reporter on adopting an M2 tumor-associated metabolic profile by coupling luciferase expression to activation of the arginase-1 promoter. After adoptive transfer in colorectal and breast mouse tumor models, the engineered macrophages migrated to the tumors and activated arginase-1 so that they could be detected by bioluminescence imaging and luciferase measured in the blood...
March 18, 2019: Nature Biotechnology
Maaz Syed-Ahmed, Mohanram Narayanan
Cardiovascular disease and infections are directly or indirectly associated with an altered immune response, which leads to a high incidence of morbidity and mortality, and together, they account for up to 70% of all deaths among patients with chronic kidney dysfunction. Impairment of the normal reaction of the innate and adaptive immune systems in chronic kidney disease predisposes patients to an increased risk of infections, virus-associated cancers, and a diminished vaccine response. On the other hand, an abnormal, exaggerated reaction of the immune systems can also occur in this group of patients, resulting in increased production and decreased clearance of proinflammatory cytokines, which can lead to inflammation and its sequelae (eg, atherosclerotic cardiovascular disease)...
January 2019: Advances in Chronic Kidney Disease
Mathieu J F Crupi, John C Bell, Ragunath Singaravelu
Cancer stem cells (CSCs) have the capacity to self-renew and differentiate to give rise to heterogenous cancer cell lineages in solid tumors. These CSC populations are associated with metastasis, tumor relapse and resistance to conventional anti-cancer therapies. Here, we focus on the use of oncolytic viruses (OVs) to target CSCs as well as the OV-driven interferon production in the tumor microenvironment (TME) that can repress CSC properties. We explore the ability of OVs to deliver combinations of immune-modulating therapeutic transgenes, such as immune checkpoint inhibitor antibodies...
March 15, 2019: Stem Cells
Laura Follia, Giulio Ferrero, Giorgia Mandili, Marco Beccuti, Daniele Giordano, Rosella Spadi, Maria Antonietta Satolli, Andrea Evangelista, Hiroyuki Katayama, Wang Hong, Amin A Momin, Michela Capello, Samir M Hanash, Francesco Novelli, Francesca Cordero
Background: Most of the patients with Pancreatic Ductal Adenocarcinoma (PDA) are not eligible for a curative surgical resection. For this reason there is an urgent need for personalized therapies. PDA is the result of complex interactions between tumor molecular profile and metabolites produced by its microenvironment. Despite recent studies identified PDA molecular subtypes, its metabolic classification is still lacking. Methods: We applied an integrative analysis on transcriptomic and genomic data of glycolytic genes in PDA...
2019: Frontiers in Oncology
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