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Monocyte/macrophage cell therapy

Tian Zhou, Zhiyi Lin, Pavan Puligujja, Diana Palandri, James Hilaire, Mariluz Araínga, Nathan Smith, Nagsen Gautam, JoEllyn McMillan, Yazen Alnouti, Xinming Liu, Benson Edagwa, Howard E Gendelman
AIM: While the  therapeutic potential for current long-acting (LA) antiretroviral therapy (ART) is undeniable, ligand-decorated nanoformulated LA-ART could optimize drug delivery to viral reservoirs. The development of decorated ART hinges, however, on formulation processes and manufacture efficiencies. To this end, we compared manufacture and purification techniques for ligand-decorated antiretroviral drug nanocrystals. MATERIALS & METHODS: Ligand-decorated nanoparticle manufacturing was tested using folic acid (FA) nanoformulated cabotegravir...
March 19, 2018: Nanomedicine
Yukio Fujiwara, Yoichi Saito, Takuya Shiota, Pan Cheng, Tsuyoshi Ikeda, Koji Ohnishi, Motohiro Takeya, Yoshihiro Komohara
Recent progress in anti-tumor therapy has revealed the significance of anti-tumor immune responses in tumor progression and clinical course in several kinds of malignant tumors. The draining lymph node is an important immune system component that contains a number of antigen-presenting cells, which induce rapid immune responses to foreign antigens. Current studies have shown that higher expression of CD169 on lymph node sinus macrophages is associated with the induction of anti-tumor immunity. In the present study, we searched for natural compounds that regulate the CD169-positive phenotype in macrophages to identify potential new anti-cancer agents targeting macrophage activation...
2018: Journal of Clinical and Experimental Hematopathology: JCEH
A Boussommier-Calleja, Y Atiyas, K Haase, M Headley, C Lewis, R D Kamm
Metastasis is the leading cause of cancer-related deaths. Recent developments in cancer immunotherapy have shown exciting therapeutic promise for metastatic patients. While most therapies target T cells, other immune cells, such as monocytes, hold great promise for therapeutic intervention. In our study, we provide primary evidence of direct engagement between human monocytes and tumor cells in a 3D vascularized microfluidic model. We first characterize the novel application of our model to investigate and visualize at high resolution the evolution of monocytes as they migrate from the intravascular to the extravascular micro-environment...
March 5, 2018: Biomaterials
Linjie Zhao, Wei Wang, Shuang Huang, Zhengnan Yang, Lian Xu, Qilian Yang, Xiu Zhou, Jinjin Wang, Qiuhong Shen, Chenlu Wang, Xiaobing Le, Min Feng, Nianxin Zhou, Wayne Bond Lau, Bonnie Lau, Shaohua Yao, Tao Yi, Xin Wang, Xia Zhao, Yuquan Wei, Shengtao Zhou
BACKGROUND: Ovarian cancer constitutes one of the most lethal gynecologic malignancies for females. Currently, early detection strategies and therapeutic options for ovarian cancer are far from satisfactory, leading to high diagnosis rates at late stages and disease relapses. New avenues of therapy are needed that target key processes in ovarian cancer progression. While a variety of non-coding RNAs have been proven to regulate ovarian cancer metastatic progression, the functional roles of RNA-binding proteins (RBPs) in this process are less well defined...
March 16, 2018: Genome Biology
Hironori Yoshino, Miyu Iwabuchi, Yuka Kazama, Maho Furukawa, Ikuo Kashiwakura
Retinoic acid-inducible gene-I (RIG-I)-like receptors (RLRs) are pattern-recognition receptors that recognize pathogen-associated molecular patterns and induce antiviral immune responses. Recent studies have demonstrated that RLR activation induces antitumor immunity and cytotoxicity against different types of cancer, including lung cancer. However a previous report has demonstrated that ionizing radiation exerts a limited effect on RLR in human monocytic cell-derived macrophages, suggesting that RLR agonists may be used as effective immunostimulants during radiation therapy...
April 2018: Oncology Letters
Denise C Hsu, Kimberly F Breglio, Luxin Pei, Chun-Shu Wong, Bruno B Andrade, Virginia Sheikh, Margery Smelkinson, Constantinos Petrovas, Adam Rupert, Leonardo Gil-Santana, Adrian Zelazny, Steven M Holland, Kenneth Olivier, Daniel Barber, Irini Sereti
Background: Immune reconstitution inflammatory syndrome (IRIS) is an aberrant inflammatory response in individuals with advanced human immunodeficiency virus (HIV) infection, after antiretroviral therapy (ART) initiation. The pathogenesis of Mycobacterium avium complex (MAC)-associated IRIS has not been fully elucidated. Methods: We investigated monocyte and CD4+ T-cell responses in vitro, tumor necrosis factor (TNF) expression in tissues, and plasma cytokines and inflammatory markers, in 13 HIV-infected patients with MAC-IRIS and 14 HIV-uninfected patients with pulmonary MAC infection...
March 10, 2018: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
Asad Nawaz, Allah Bakhsh Javaid, Sana Irshad, Seyed Hossein Hoseinifar, Hanguo Xiong
The gut immune system is, the main option for maintaining host's health, affected by numerous factors comprising dietary constituents and commensal bacteria. These dietary components that affect the intestinal immunity and considered as an alternative of antibiotics are called immunosaccharides. Fructooligosaccharide (FOS), Galactooligosaccharide (GOS), inulin, dietary carbohydrates, and xylooligosaccharide (XOS) are among the most studied prebiotics in human as well as in aquaculture. Although prebiotics and probiotics have revealed potential as treatment for numerous illnesses in both human and fish, a comprehensive understanding of the molecular mechanism behind direct and indirect effect on the intestinal immune response will help more and perhaps extra effective therapy intended for ailments...
March 3, 2018: Fish & Shellfish Immunology
D Henrich, C Seebach, R Verboket, A Schaible, I Marzi, H Bonig
Bone marrow mononuclear cells (BMC) seeded on a scaffold of β-tricalcium phosphate (β-TCP) promote bone healing in a critical-size femur defect model. Being BMC a mixed population of predominantly mature haematopoietic cells, which cell type(s) is(are) instrumental for healing remains elusive. Although clinical therapies using BMC are often dubbed as stem cell therapies, whether stem cells are relevant for the therapeutic effects is unclear and, at least in the context of bone repair, seems dubious. Instead, in light of the critical contribution of monocytes and macrophages to tissue development, homeostasis and injury repair, in the current study it was hypothesised that BMC-mediated bone healing derived from the stem cell population...
March 6, 2018: European Cells & Materials
Liang Liu, Lin Yang, Wei Yan, Jing Zhai, Donald Pizzo, Peiguo Chu, Andrew R Chin, Meng Shen, Chuan Dong, Xianhui Ruan, Xiubao Ren, George Somlo, Shizhen Emily Wang
PURPOSE: Preoperative or neoadjuvant therapy (NT) is increasingly used in patients with locally advanced or inflammatory breast cancer (BC) to allow optimal surgery and aim for pathological response. However, many BCs are resistant or relapse after treatment. Here, we investigated conjunctive chemotherapy-triggered events occurring systemically and locally, potentially promoting a cancer stem-like cell (CSC) phenotype and contributing to tumor relapse. EXPERIMENTAL DESIGN: We started by comparing the effect of paired pre- and post-NT patient sera on the CSC properties of BC cells...
March 2, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Xi Li, Qianwen Jin, Qunyan Yao, Beili Xu, Lixin Li, Shuncai Zhang, Chuantao Tu
At present, there are no effective antifibrotic drugs for patients with chronic liver disease; hence, the development of antifibrotic therapies is urgently needed. Here, we performed an experimental and translational study to investigate the potential and underlying mechanism of quercetin treatment in liver fibrosis, mainly focusing on the impact of quercetin on macrophages activation and polarization. BALB/c mice were induced liver fibrosis by carbon tetrachloride (CCl4 ) for 8 weeks and concomitantly treated with quercetin (50 mg/kg) or vehicle by daily gavage...
2018: Frontiers in Pharmacology
Maria Diedrichs-Möhring, Ulrike Kaufmann, Gerhild Wildner
Autoimmune diseases usually follow a relapsing-remitting or a chronic progressive course. To understand the underlying immunopathogenesis we investigated experimental Lewis rat models displaying both disease types, which were only dependent on the autoantigen peptide used for immunization. Retinal S-Antigen-peptide PDSAg induces chronic, monophasic disease, whilst interphotoreceptor retinoid-binding protein (IRBP)-peptide R14 causes a spontaneously relapsing-remitting course. R14-mediated uveitis can be re-induced by immunization; PDSAg-induced disease is even preventable by prior CFA-injection...
February 26, 2018: Progress in Retinal and Eye Research
Wei Liu, Matyas Molnar, Carolyn Garnham, Heval Benav, Helge Rask-Andersen
The human inner ear, which is segregated by a blood/labyrinth barrier, contains resident macrophages [CD163, ionized calcium-binding adaptor molecule 1 (IBA1)-, and CD68-positive cells] within the connective tissue, neurons, and supporting cells. In the lateral wall of the cochlea, these cells frequently lie close to blood vessels as perivascular macrophages. Macrophages are also shown to be recruited from blood-borne monocytes to damaged and dying hair cells induced by noise, ototoxic drugs, aging, and diphtheria toxin-induced hair cell degeneration...
2018: Frontiers in Immunology
Mate Kiss, Sofie Van Gassen, Kiavash Movahedi, Yvan Saeys, Damya Laoui
Tumors of various histological origins show abundant infiltration of myeloid cells from early stages of disease progression. These cells have a profound impact on antitumor immunity and influence fundamental processes that underlie malignancy, including neoangiogenesis, sustained cancer cell proliferation, metastasis and therapy resistance. For these reasons, development of therapeutic approaches to deplete or reprogram myeloid cells in cancer is an emerging field of interest. However, knowledge about the heterogeneity of myeloid cells in tumors and their variability between patients and disease stages is still limited...
February 14, 2018: Cellular Immunology
Digdem Yoyen-Ermis, Kivilcim Ozturk-Atar, Muammer Alper Kursunel, Cisel Aydin, Didem Ozkazanc, Mustafa G Uuml Rb Uuml Z, Aysegul Uner, Metin Tulu, Sema Calis, Gunes Esendagli
While reshaping its microenvironment, tumors are also capable of influencing systemic processes such as myeloid cell production. Therefore, the tumor-induced myeloid cells, such as myeloid-derived suppressor cells (MDSCs) which are characterized with pro-cancer properties, became another target in order to increase success of the therapy. This study evaluated the capacity of a novel dendrimeric drug delivery platform to eliminate tumor-induced myeloid cells. As described in a previous study by our research group, the anti-Flt1 antibody-conjugated polyethylene glycol (PEG)-cored poly(amidoamine) (PAMAM) dendrimers improved the efficacy of gemcitabine against pancreatic cancer...
February 26, 2018: Molecular Pharmaceutics
Sofia P Rebelo, Catarina Pinto, Tatiana R Martins, Nathalie Harrer, Marta F Estrada, Pablo Loza-Alvarez, José Cabeçadas, Paula M Alves, Emilio J Gualda, Wolfgang Sommergruber, Catarina Brito
The tumour microenvironment (TME) shapes disease progression and influences therapeutic response. Most aggressive solid tumours have high levels of myeloid cell infiltration, namely tumour associated macrophages (TAM). Recapitulation of the interaction between the different cellular players of the TME, along with the extracellular matrix (ECM), is critical for understanding the mechanisms underlying disease progression. This particularly holds true for prediction of therapeutic response(s) to standard therapies and interrogation of efficacy of TME-targeting agents...
May 2018: Biomaterials
Bridget S Fisher, Richard R Green, Rachel R Brown, Matthew P Wood, Tiffany Hensley-McBain, Cole Fisher, Jean Chang, Andrew D Miller, William J Bosche, Jeffrey D Lifson, Maud Mavigner, Charlene J Miller, Michael Gale, Guido Silvestri, Ann Chahroudi, Nichole R Klatt, Donald L Sodora
Liver disease is a leading contributor to morbidity and mortality during HIV infection, despite the use of combination antiretroviral therapy (cART). The precise mechanisms of liver disease during HIV infection are poorly understood partially due to the difficulty in obtaining human liver samples as well as the presence of confounding factors (e.g. hepatitis co-infection, alcohol use). Utilizing the simian immunodeficiency virus (SIV) macaque model, a controlled study was conducted to evaluate the factors associated with liver inflammation and the impact of cART...
February 21, 2018: PLoS Pathogens
Jonathon H Gralewski, Ginell R Post, Frits van Rhee, Youzhong Yuan
BACKGROUND: Plasma cell myeloma (PCM) is a neoplasm of terminally differentiated B lymphocytes with molecular heterogeneity. Although therapy-related myeloid neoplasms are common in plasma cell myeloma patients after chemotherapy, transdifferentiation of plasma cell myeloma into myeloid neoplasms has not been reported in literature. Here we report a very rare case of myeloid neoplasm transformed from plasma cell myeloma. CASE PRESENTATION: A 60-year-old man with a history of plasma cell myeloma with IGH-MAF gene rearrangement and RAS/RAF mutations developed multiple soft tissue lesions one year following melphalan-based chemotherapy and autologous stem cell transplant...
February 20, 2018: Diagnostic Pathology
Asami Hanazawa, Ryoji Ito, Ikumi Katano, Kenji Kawai, Motohito Goto, Hiroshi Suemizu, Yutaka Kawakami, Mamoru Ito, Takeshi Takahashi
The tumor microenvironment contains unique immune cells, termed myeloid-derived suppressor cells (MDSCs), and tumor-associated macrophages (TAMs) that suppress host anti-tumor immunity and promote tumor angiogenesis and metastasis. Although these cells are considered a key target of cancer immune therapy, in vivo animal models allowing differentiation of human immunosuppressive myeloid cells have yet to be established, hampering the development of novel cancer therapies. In this study, we established a novel humanized transgenic (Tg) mouse strain, human interleukin (hIL)-6-expressing NOG mice (NOG-hIL-6 transgenic mice)...
2018: Frontiers in Immunology
Shuhong Han, Haoyang Zhuang, Stepan Shumyak, Jingfan Wu, Chao Xie, Hui Li, Li-Jun Yang, Westley H Reeves
The generation of CD138+ phagocytic macrophages with an alternative (M2) phenotype that clear apoptotic cells from tissues is defective in lupus. Liver X receptor-alpha (LXRα) is an oxysterol-regulated transcription factor that promotes reverse cholesterol transport and alternative (M2) macrophage activation. Conversely, hypoxia-inducible factor 1-α (HIF1α) promotes classical (M1) macrophage activation. The objective of this study was to see if lupus can be treated by enhancing the generation of M2-like macrophages using LXR agonists...
2018: Frontiers in Immunology
Frank Vari, David Arpon, Colm Keane, Mark S Hertzberg, Dipti Talaulikar, Sanjiv Jain, Qingyan Cui, Erica Han, Josh Tobin, Robert Bird, Donna Cross, Annette Hernandez, Clare Gould, Simone Birch, Maher K Gandhi
Much focus has been on the interaction of PD-L1 on malignant B-cells with PD-1 on effector T-cells in inhibiting anti-lymphoma immunity. We sought to establish the contribution of NK-cells and inhibitory CD163+ monocytes/macrophages in Hodgkin Lymphoma (cHL) and Diffuse Large B-cell Lymphoma (DLBCL). Levels of PD-1 on NK-cells were elevated in cHL relative to DLBCL. Notably, CD3- CD56hi CD16-ve NK-cells had substantially higher PD-1 expression relative to CD3- CD56dim CD16+ cells, and were expanded in blood and tissue, more marked in cHL than DLBCL patients...
February 15, 2018: Blood
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