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Myeloid regulatory cells

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https://www.readbyqxmd.com/read/29238707/drug-repurposing-for-the-treatment-of-acute-myeloid-leukemia
#1
REVIEW
Vibeke Andresen, Bjørn T Gjertsen
Acute myeloid leukemia (AML) is a heterogeneous disease characterized by the accumulation of immature myeloid progenitor cells in the bone marrow, compromising of normal blood cell production and ultimately resulting in bone marrow failure. With a 20% overall survival rate at 5 years and 50% in the 18- to 65-year-old age group, new medicines are needed. It is proposed that development of repurposed drugs may be a part of the new therapy needed. AML is subdivided into recurrent molecular entities based on molecular genetics increasingly accessible for precision medicine...
2017: Frontiers in Medicine
https://www.readbyqxmd.com/read/29230377/clinical-significance-of-circulating-immune-cells-in-left-and-right-sided-colon-cancer
#2
Jiabo Di, Meng Zhuang, Hong Yang, Beihai Jiang, Zaozao Wang, Xiangqian Su
Background: Left-sided and right-sided colon cancers (LCCs and RCCs, respectively) differ in their epidemiology, pathogenesis, genetic and epigenetic alterations, molecular pathways and prognosis. Notably, immune response gene expression profiles have been shown to differ between patients with LCC and patients with RCC. The immune system plays an important role in tumor immunosurveillance, and there is increasing evidence that peripheral blood immune cells have a profound influence on tumor prognosis...
2017: PeerJ
https://www.readbyqxmd.com/read/29228706/pharmacological-rac1-inhibitors-with-selective-apoptotic-activity-in-human-acute-leukemic-cell-lines
#3
Maia Cabrera, Emiliana Echeverria, Federico Remes Lenicov, Georgina Cardama, Nazareno Gonzalez, Carlos Davio, Natalia Fernández, Pablo Lorenzano Menna
Rac1 GTPase has long been recognized as a critical regulatory protein in different cellular and molecular processes involved in cancer progression, including acute myeloid leukemia. Here we show the antitumoral activity of ZINC69391 and 1A-116, two chemically-related Rac1 pharmacological inhibitors, on a panel of four leukemic cell lines representing different levels of maturation. Importantly, we show that the main mechanism involved in the antitumoral effect triggered by the Rac1 inhibitors comprises the induction of the mitochondrial or intrinsic apoptotic pathway...
November 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29225603/regulatory-t-cells-suppress-inflammation-and-blistering-in-pemphigoid-diseases
#4
Katja Bieber, Shijie Sun, Mareike Witte, Anika Kasprick, Foteini Beltsiou, Martina Behnen, Tamás Laskay, Franziska S Schulze, Elena Pipi, Niklas Reichhelm, René Pagel, Detlef Zillikens, Enno Schmidt, Tim Sparwasser, Kathrin Kalies, Ralf J Ludwig
Regulatory T cells (Tregs) are well known for their modulatory functions in adaptive immunity. Through regulation of T cell functions, Tregs have also been demonstrated to indirectly curb myeloid cell-driven inflammation. However, direct effects of Tregs on myeloid cell functions are insufficiently characterized, especially in the context of myeloid cell-mediated diseases, such as pemphigoid diseases (PDs). PDs are caused by autoantibodies targeting structural proteins of the skin. Autoantibody binding triggers myeloid cell activation through specific activation of Fc gamma receptors, leading to skin inflammation and subepidermal blistering...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29221109/protein-phosphatase-4-regulatory-subunit-2-ppp4r2-is-recurrently-deleted-in-acute-myeloid-leukemia-and-required-for-efficient-dna-double-strand-break-repair
#5
Julia K Herzig, Lars Bullinger, Alpaslan Tasdogan, Philipp Zimmermann, Martin Schlegel, Veronica Teleanu, Daniela Weber, Frank G Rücker, Peter Paschka, Anna Dolnik, Edith Schneider, Florian Kuchenbauer, Florian H Heidel, Christian Buske, Hartmut Döhner, Konstanze Döhner, Verena I Gaidzik
We have previously identified a recurrent deletion at chromosomal band 3p14.1-p13 in patients with acute myeloid leukemia (AML). Among eight protein-coding genes, this microdeletion affects the protein phosphatase 4 regulatory subunit 2 (PPP4R2), which plays an important role in DNA damage response (DDR). Investigation of mRNA expression during murine myelopoiesis determined that Ppp4r2 is higher expressed in more primitive hematopoietic cells. PPP4R2 expression in primary AML samples compared to healthy bone marrow was significantly lower, particularly in patients with 3p microdeletion or complex karyotype...
November 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29215754/inhibition-of-jak2-stat3-reduces-tumor-induced-angiogenesis-and-myeloid-derived-suppressor-cells-in-head-and-neck-cancer
#6
Jian-Feng Liu, Wei-Wei Deng, Lei Chen, Yi-Cun Li, Lei Wu, Si-Rui Ma, Wen-Feng Zhang, Lin-Lin Bu, Zhi-Jun Sun
Angiogenesis is an essential event in tumor growth and metastasis, and immune system also contributes to the tumor evasion. Emerging evidences have suggested the bidirectional link between angiogenesis and immunosuppression. Myeloid-derived suppressor cell (MDSC) is a kind of immunosuppressive cells and plays an important role in this process. However, the actual regulatory mechanisms of angiogenesis and MDSCs in head and neck squamous cell carcinoma (HNSCC) were unclear. In this study, through analyzing the immunohistochemistry staining of human HNSCC tissue microarray, we found that the microvascular density (MVD) was significantly increased in HNSCC patients...
December 7, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/29209091/type-i-interferons-drive-inflammasome-independent-emergency-monocytopoiesis-during-endotoxemia
#7
Corentin Lasseaux, Marie-Pierre Fourmaux, Mathias Chamaillard, Lionel Franz Poulin
Emergency monocytopoiesis is an inflammation-driven hematological process that supplies the periphery with monocytes and subsequently with macrophages and monocyte-derived dendritic cells. Yet, the regulatory mechanisms by which early bone marrow myeloid progenitors commit to monocyte-derived phagocytes during endotoxemia remains elusive. Herein, we show that type I interferons signaling promotes the differentiation of monocyte-derived phagocytes at the level of their progenitors during a mouse model of endotoxemia...
December 5, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29206151/an-overview-of-l-amino-acid-oxidase-functions-from-bacteria-to-mammals-focus-on-the-immunoregulatory-phenylalanine-oxidase-il4i1
#8
REVIEW
Flavia Castellano, Valérie Molinier-Frenkel
l-amino acid oxidases are flavin adenine dinucleotide-dependent enzymes present in all major kingdom of life, from bacteria to mammals. They participate in defense mechanisms by limiting the growth of most bacteria and parasites. A few mammalian LAAOs have been described, of which the enzyme "interleukin-4 induced gene 1" (IL4I1) is the best characterized. IL4I1 mainly oxidizes l-phenylalanine. It is a secreted enzyme physiologically produced by antigen presenting cells of the myeloid and B cell lineages and T helper type (Th) 17 cells...
December 5, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29204699/therapeutic-reduction-of-cell-mediated-immunosuppression-in-mycosis-fungoides-and-s%C3%A3-zary-syndrome
#9
Larisa J Geskin, Oleg E Akilov, Soonyou Kwon, Michael Schowalter, Simon Watkins, Theresa L Whiteside, Lisa H Butterfield, Louis D Falo
Tumor progression is associated with progressive immunosuppression mediated in part by T regulatory cell(s) (Treg) and/or myeloid-derived suppressor cell(s) (MDSC). Development of strategies to reduce populations of immune cells with suppressive function in cancer patients may enable the induction or recovery of immunity against tumor cells, which may limit or reverse disease progression. With a goal of developing Treg and MDSC neutralizing strategies to treat mycosis fungoides (MF) and Sézary syndrome (SzS), we determined the association between disease stage and suppressor cell populations in patients with MF/SzS, including those responding to therapy...
December 4, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/29203226/innately-versatile-%C3%AE-%C3%AE-17%C3%A2-t-cells-in-inflammatory-and-autoimmune-diseases
#10
REVIEW
Pedro H Papotto, Annika Reinhardt, Immo Prinz, Bruno Silva-Santos
IL-17-producing γδ (γδ17) T cells form a versatile subset of cells that respond rapidly to innate stimuli and support the pro-inflammatory functions of different myeloid and lymphoid lineages, being particularly critical in the early stages of inflammatory and autoimmune responses. In mice, under homeostatic conditions, these innate-like lymphocytes are pre-programmed in the fetal thymus, through an intricate process involving both T cell receptor-dependent and -independent signals, which allows them to readily produce IL-17 upon stimulation...
December 1, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/29193231/using-mri-cell-tracking-to-monitor-immune-cell-recruitment-in-response-to-a-peptide-based-cancer-vaccine
#11
Marie-Laurence Tremblay, Christa Davis, Chris V Bowen, Olivia Stanley, Cathryn Parsons, Genevieve Weir, Mohan Karkada, Marianne M Stanford, Kimberly D Brewer
PURPOSE: MRI cell tracking can be used to monitor immune cells involved in the immunotherapy response, providing insight into the mechanism of action, temporal progression of tumor growth, and individual potency of therapies. To evaluate whether MRI could be used to track immune cell populations in response to immunotherapy, CD8+ cytotoxic T cells, CD4+ CD25+ FoxP3+ regulatory T cells, and myeloid-derived suppressor cells were labeled with superparamagnetic iron oxide particles. METHODS: Superparamagnetic iron oxide-labeled cells were injected into mice (one cell type/mouse) implanted with a human papillomavirus-based cervical cancer model...
November 29, 2017: Magnetic Resonance in Medicine: Official Journal of the Society of Magnetic Resonance in Medicine
https://www.readbyqxmd.com/read/29192243/autonomous-feedback-loop-of-runx1-p53-cbfb-in-acute-myeloid-leukemia-cells
#12
Ken Morita, Mina Noura, Chieko Tokushige, Shintaro Maeda, Hiroki Kiyose, Gengo Kashiwazaki, Junichi Taniguchi, Toshikazu Bando, Kenichi Yoshida, Toshifumi Ozaki, Hidemasa Matsuo, Seishi Ogawa, Pu Paul Liu, Tatsutoshi Nakahata, Hiroshi Sugiyama, Souichi Adachi, Yasuhiko Kamikubo
Although runt-related transcription factor 1 (RUNX1) and its associating core binding factor-β (CBFB) play pivotal roles in leukemogenesis, and inhibition of RUNX1 has now been widely recognized as a novel strategy for anti-leukemic therapies, it has been elusive how leukemic cells could acquire the serious resistance against RUNX1-inhibition therapies and also whether CBFB could participate in this process. Here, we show evidence that p53 (TP53) and CBFB are sequentially up-regulated in response to RUNX1 depletion, and their mutual interaction causes the physiological resistance against chemotherapy for acute myeloid leukemia (AML) cells...
November 30, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29190690/development-of-effective-tumor-immunotherapy-using-a-novel-dendritic-cell-targeting-toll-like-receptor-ligand
#13
Nadeeka H De Silva, Takashi Akazawa, Viskam Wijewardana, Norimitsu Inoue, Maremichi Oyamada, Atsuko Ohta, Yuki Tachibana, Daluthgamage Patsy H Wijesekera, Mitsuru Kuwamura, Yasuko Nishizawa, Kazuyuki Itoh, Takeshi Izawa, Shingo Hatoya, Tetsuya Hasegawa, Jyoji Yamate, Toshio Inaba, Kikuya Sugiura
Although dendritic cell (DC)-based immunotherapy shows little toxicity, improvements should be necessary to obtain satisfactory clinical outcome. Using interferon-gamma injection along with DCs, we previously obtained significant clinical responses against small or early stage malignant tumors in dogs. However, improvement was necessary to be effective to largely developed or metastatic tumors. To obtain effective methods applicable to those tumors, we herein used a DC-targeting Toll-like receptor ligand, h11c, and examined the therapeutic effects in murine subcutaneous and visceral tumor models and also in the clinical treatment of canine cancers...
2017: PloS One
https://www.readbyqxmd.com/read/29189485/myeloid-derived-suppressor-cells-and-their-potential-application-in-transplantation
#14
Joseph R Scalea, Young Lee, Eduardo Davila, Jonathan S Bromberg
Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of immunosuppressive cells of the myeloid lineage upregulated by mediators of inflammation such as IL-2, GCSF, and S100A8/A9. These cells have been studied extensively by tumor biologists. Because of their robust immunosuppressive potential, MDSCs have stirred recent interest among transplant immunologists as well. MDSCs inhibit T cell responses through, among other mechanisms, the activity of arginase-1 and iNOS, and the expansion of T regulatory (Treg) cells...
November 20, 2017: Transplantation
https://www.readbyqxmd.com/read/29184980/blockage-of-the-nlrp3-inflammasome-by-mcc950-improves-anti-tumor-immune-responses-in-head-and-neck-squamous-cell-carcinoma
#15
Lei Chen, Cong-Fa Huang, Yi-Cun Li, Wei-Wei Deng, Liang Mao, Lei Wu, Wen-Feng Zhang, Lu Zhang, Zhi-Jun Sun
The NLRP3 inflammasome is a critical innate immune pathway responsible for producing active interleukin (IL)-1β, which is associated with tumor development and immunity. However, the mechanisms regulating the inflammatory microenvironment, tumorigenesis and tumor immunity are unclear. Herein, we show that the NLRP3 inflammasome was over-expressed in human HNSCC tissues and that the IL-1β concentration was increased in the peripheral blood of HNSCC patients. Additionally, elevated NLRP3 inflammasome levels were detected in tumor tissues of Tgfbr1/Pten 2cKO HNSCC mice, and elevated IL-1β levels were detected in the peripheral blood serum, spleen, draining lymph nodes and tumor tissues...
November 28, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/29182438/high-numbers-of-myeloid-derived-suppressor-cells-in-peripheral-blood-and-ascitic-fluid-of-cirrhotic-and-hcc-patients
#16
Nadia Elwan, Mohamed Labib Salem, Abdelrahman Kobtan, Ferial El-Kalla, Loai Mansour, Mohamed Yousef, Ashraf Al-Sabbagh, Abdel-Aziz A Zidan, Sherief Abd-Elsalam
BACKGROUND: Hepatocellular carcinoma (HCC) is the 3rd most common cause of cancer-related death worldwide. It has evolved different immune escape mechanisms, which might include emergence of lymphoid and myeloid regulatory cells. Aim of this work: To determine the numbers of Myeloid-derived suppressor cells (MDSCs) in peripheral blood and ascitic fluid in cirrhosis and HCC and their relation to IFN-γ and α-fetoprotein (α-FP). PATIENTS AND METHODS: Sixty individuals were enrolled in this study; forty cirrhotic patients with ascites; twenty without HCC (Group I), and twenty with HCC (group II) as well as twenty healthy individuals as a control group (group III)...
November 28, 2017: Immunological Investigations
https://www.readbyqxmd.com/read/29177902/effect-of-native-and-modified-apolipoprotein-a-i-on-dna-synthesis-in-cultures-of-different-cells
#17
I F Usynin, A N Dudarev, S M Miroshnichenko, T A Tkachenko, A Yu Gorodetskaya
Culturing of bone marrow cells in serum-free RPMI-1640 medium for 24 h was accompanied by a decrease in the rate of [3H]-thymidine incorporation into DNA. Addition of native apolipoprotein A-I (apoA-I) or plasma LDL and HDL to the culture medium increased this parameter. In contrast to native apoA-I, its modified form decelerated DNA synthesis in bone marrow cells. A similar inhibitory effect of modified protein was observed in cultures of human embryonic kidney cells (HEK293) and in rapidly proliferating mouse macrophage cell line ANA-1...
November 25, 2017: Bulletin of Experimental Biology and Medicine
https://www.readbyqxmd.com/read/29175333/distinct-roles-of-rheb-and-raptor-in-activating-mtor-complex-1-for-the-self-renewal-of-hematopoietic-stem-cells
#18
Hui Peng, Atsuo Kasada, Masaya Ueno, Takayuki Hoshii, Yuko Tadokoro, Naho Nomura, Chiaki Ito, Yusuke Takase, Ha Thi Vu, Masahiko Kobayashi, Bo Xiao, Paul F Worley, Atsushi Hirao
The mammalian target of rapamycin (mTOR) complex 1 (mTORC1) senses a cell's energy status and environmental levels of nutrients and growth factors. In response, mTORC1 mediates signaling that controls protein translation and cellular metabolism. Although mTORC1 plays a critical role in hematopoiesis, it remains unclear which upstream stimuli regulate mTORC1 activity in the context of hematopoietic stem cells (HSC) maintenance in vivo. In this study, we investigated the function of Rheb, a critical regulator of mTORC1 activity controlled by the PI3K-AKT-TSC axis, both in HSC maintenance in mice at steady-state and in HSC-derived hematopoiesis post-transplantation...
November 21, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29172279/anti-vascular-endothelial-growth-factor-targeting-by-curcumin-and-thalidomide-in-acute-myeloid-leukemia-cells
#19
Mahdieh Salemi, Saeed Mohammadi, Ardeshir Ghavamzadeh, Mohsen Nikbakht
Acute myeloid leukemias (AMLs) are blood disorders that exhibit uncontrolled growth and reduction of apoptosis rates. As with other malignancies, progression may be result of induction and formation of new blood vessels influenced by disease conditions. Cancer cells produce a variety of factors which play important roles in angiogenesis. Vascular endothelial growth factor (VEGF) is critical for many malignancies, including AMLs. Curcumin, as a natural compound, is able to enhance apoptosis via a mechanism affecting regulatory genes...
November 26, 2017: Asian Pacific Journal of Cancer Prevention: APJCP
https://www.readbyqxmd.com/read/29171115/carboplatin-and-programmed-death-ligand-1-blockade-synergistically-produce-a-similar-antitumor-effect-to-carboplatin-alone-in-murine-id8-ovarian-cancer-model
#20
Xinxin Zhu, Jia Xu, Han Cai, Jinghe Lang
AIM: In advanced, platinum resistant or refractory ovarian cancer (OC), the therapeutic efficacy of carboplatin is controversial. Although anti-programmed death-1/programmed death-ligand 1 (PD-1/PD-L1) pathway blockages show great potential in cancer treatment, the antitumor effect of single anti-PD-L1 pathway monoclonal antibody (mAb) is not obvious in advanced or some poorly immunogenic tumors, including OC. We compared the effects of single or combined carboplatin and anti-PD-L1 mAb treatments and explored the possible antitumor mechanisms in a murine ID8 OC model...
November 24, 2017: Journal of Obstetrics and Gynaecology Research
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