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Myeloid-derived suppressor cells

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https://www.readbyqxmd.com/read/29230664/cd14-%C3%A2-hla-dr-low-mdscs-are-elevated-in-the-periphery-of-early-stage-breast-cancer-patients-and-suppress-autologous-t-cell-proliferation
#1
Lisa Speigl, Helen Burow, Jithendra Kini Bailur, Nicole Janssen, Christina-Barbara Walter, Graham Pawelec, Christopher Shipp
PURPOSE: Despite the recent expansion in the use of immunotherapy for many cancer types, it is still not a standard treatment for breast cancer. Identifying differences in the immune systems of breast cancer patients compared to healthy women might provide insight into potential targets for immunotherapy and thus may assist its clinical implementation. METHODS: Multi-colour flow cytometry was used to investigate myeloid and lymphoid populations in the peripheral blood of breast cancer patients (n = 40) and in the blood of healthy age-matched women (n = 25)...
December 11, 2017: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/29227812/overexpression-of-arginase-1-is-linked-to-dnmt3a-and-tet2-mutations-in-lower-grade-myelodysplastic-syndromes-and-chronic-myelomonocytic-leukemia
#2
A H Cull, D Mahendru, B Snetsinger, D Good, K Tyryshkin, A Chesney, Z Ghorab, M Reis, R Buckstein, R A Wells, M J Rauh
Immune dysregulation is a common feature of myelodysplastic syndromes (MDS) and chronic myelomonocytic leukemia (CMML), particularly in early stages. However, the genetic basis remains poorly understood. We recently reported that macrophages from mice deficient in tet methylcytosine dioxygenase 2 (Tet2), a model of MDS/CMML, are hyperinflammatory and have increased expression of arginase 1 (Arg1). In macrophages and myeloid derived suppressor cells (MDSCs) expression of Arg1 contributes to T-cell suppression and immune evasion by L-arginine depletion, in the setting of chronic inflammation and cancer...
December 6, 2017: Leukemia Research
https://www.readbyqxmd.com/read/29226090/inhibition-of-il-18-mediated-myeloid-derived-suppressor-cell-accumulation-enhances-anti-pd1-efficacy-against-osteosarcoma-cancer
#3
Ying Guan, Rui Zhang, Zhibin Peng, Daming Dong, Guojun Wei, Yansong Wang
Myeloid derived suppressor cells (MDSC) are very important in tumor immune evasion and they dramatically increased in peripheral blood of patients with osteosarcoma cancer. The association between MDSC and various cytokines has been studied in the peripheral blood. However, little is known about the mechanism drawing MDSC into tumor parenchyma. This study was to analyze the correlation between MDSC subsets and interleukin 18 (IL-18) level in osteosarcoma tumor model and its effect on the immunotherapy. MDSC were isolated from the blood and parenchyma and analyzed in the osteosarcoma tumor model...
November 2017: Journal of Bone Oncology
https://www.readbyqxmd.com/read/29225343/advances-in-the-understanding-and-treatment-of-sepsis-induced-immunosuppression
#4
REVIEW
Fabienne Venet, Guillaume Monneret
Sepsis is defined as a life-threatening organ dysfunction that is caused by a dysregulated host response to infection. Sepsis can induce acute kidney injury and multiple organ failures and represents the most common cause of death in the intensive care unit. Sepsis initiates a complex immune response that varies over time, with the concomitant occurrence of both pro-inflammatory and anti-inflammatory mechanisms. As a result, most patients with sepsis rapidly display signs of profound immunosuppression, which is associated with deleterious consequences...
December 11, 2017: Nature Reviews. Nephrology
https://www.readbyqxmd.com/read/29222071/hdac11-is-a-regulator-of-diverse-immune-functions
#5
REVIEW
Cansu Yanginlar, Colin Logie
Histone deacetylases deacetylate histone and non-histone protein targets. Aberrant HDAC expression and function have been observed in several diseases, which makes these enzymes attractive treatment targets. Here, we summarize recent literature that addresses the roles of HDAC11 on the regulation of different immune cells including neutrophils, myeloid derived suppressor cells and T-cells. HDAC11 was initially identified as a negative regulator of the well-known anti-inflammatory cytokine IL-10. Hence, antagonizing HDAC11 activity may have anti-tumor potential, whereas activating HDAC11 may be useful to treat chronic inflammation or autoimmunity...
December 5, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29221113/the-peripheral-immune-status-of-granulocytic-myeloid-derived-suppressor-cells-correlates-the-survival-in-advanced-gastric-cancer-patients-receiving-cisplatin-based-chemotherapy
#6
Hirokazu Shoji, Kohei Tada, Shigehisa Kitano, Takashi Nishimura, Yasuhiro Shimada, Kengo Nagashima, Kazunori Aoki, Nobuyoshi Hiraoka, Yoshitaka Honma, Satoru Iwasa, Atsuo Takashima, Ken Kato, Narikazu Boku, Kazufumi Honda, Tesshi Yamada, Yuji Heike, Tetsuya Hamaguchi
Background: The prognostic significance of peripheral immune status in patients with advanced gastric cancer (AGC) remains unclear. Results: From July 2013 through December 2014, 37 patients were enrolled. Among patients with 25 subsets of immune cells, patients in the high group of granulocytic myeloid-derived suppressor cells (Gr-MDSCs) showed significantly shorter progression-free survival (PFS) than those in the low group (3.98 vs. 8.78 months; hazards ratio (HR), 2...
November 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29218828/monocytic-myeloid-derived-suppressor-cells-as-prognostic-factor-in-chronic-myeloid-leukaemia-patients-treated-with-dasatinib
#7
Cesarina Giallongo, Nunziatina L Parrinello, Piera La Cava, Giuseppina Camiolo, Alessandra Romano, Marina Scalia, Fabio Stagno, Giuseppe A Palumbo, Roberto Avola, Giovanni Li Volti, Daniele Tibullo, Francesco Di Raimondo
Myeloid suppressor cells are a heterogeneous group of myeloid cells that are increased in patients with chronic myeloid leukaemia (CML) inducing T cell tolerance. In this study, we found that therapy with tyrosine kinase inhibitors (TKI) decreased the percentage of granulocytic MDSC, but only patients treated with dasatinib showed a significant reduction in the monocytic subset (M-MDSC). Moreover, a positive correlation was observed between number of persistent M-MDSC and the value of major molecular response in dasatinib-treated patients...
December 8, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/29218366/haploidentical-natural-killer-cells-induce-remissions-in-non-hodgkin-lymphoma-patients-with-low-levels-of-immune-suppressor-cells
#8
Veronika Bachanova, Dhifaf Sarhan, Todd E DeFor, Sarah Cooley, Angela Panoskaltsis-Mortari, Bruce R Blazar, Julie M Curtsinger, Linda Burns, Daniel J Weisdorf, Jeffrey S Miller
We report a novel phase 2 clinical trial in patients with poor prognosis refractory non-Hodgkin lymphoma (NHL) testing the efficacy of haploidentical donor natural killer (NK) cell therapy (NK dose 0.5-3.27 × 107 NK cells/kg) with rituximab and IL-2 (clinicaltrials.gov NCT01181258). Therapy was tolerated without graft-versus-host disease, cytokine release syndrome, or neurotoxicity. Of 14 evaluable patients, 4 had objective responses (29%; 95% CI 12-55%) at 2 months: 2 had complete response lasting 3 and 9 months...
December 7, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/29216804/the-use-of-alpha-fetoprotein-for-the-treatment-of-autoimmune-diseases-and-cancer
#9
Vladimir N Pak
Alpha-fetoprotein is a shuttle protein that delivers nutrients through receptor-mediated endocytosis to embryotic cells. In adults, alpha-fetoprotein can shuttle drugs into alpha-fetoprotein receptor-positive myeloid-derived suppressor, regenerating and also cancer cells. Drugs with high-binding affinity to alpha-fetoprotein can activate or deplete targeted cells. Myeloid-derived suppressor cells activation leads to immune suppression that can be used for treating autoimmune diseases. On the other hand, toxins delivered by alpha-fetoprotein can damage myeloid-derived suppressor cells and consequently unleash innate and adaptive immunity to destroy cancer cells...
January 2018: Therapeutic Delivery
https://www.readbyqxmd.com/read/29215754/inhibition-of-jak2-stat3-reduces-tumor-induced-angiogenesis-and-myeloid-derived-suppressor-cells-in-head-and-neck-cancer
#10
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/29211299/endoplasmic-reticulum-stress-induced-lox-1-cd15-polymorphonuclear-myeloid-derived-suppressor-cells-in-hepatocellular-carcinoma
#11
Nan Jiang, Yan-Fang Xing, Bo Hu, Jian-Xin Tang, Hui-Min Dong, Yu-Mei He, Dan-Yun Ruan, Qing-Jian Ye, Jia-Rong Cai, Xiao-Kun Ma, Jie Chen, Xiu-Rong Cai, Ze-Xiao Lin, Xiang-Yuan Wu, Xing Li
AIM: A recent study indicated that Lectin-type oxidized LDL receptor-1 (LOX-1) was a distinct surface marker for human polymorphonuclears myeloid-derived suppressor cells (PMN-MDSC). The present study was aimed to investigate the existence LOX-1 PMN-MDSC in hepatocellular carcinoma (HCC) patients. METHODS: 127 HCC patients, 10 patients with mild active chronic hepatits B, 10 liver cirrhosis due to hepatitis B, 10 liver dysplastic node with hepatitis B and 50 health control were included...
December 6, 2017: Immunology
https://www.readbyqxmd.com/read/29208938/oncolytic-virotherapy-as-an-immunotherapeutic-strategy-for-multiple-myeloma
#12
REVIEW
Daniel E Meyers, Satbir Thakur, Chandini M Thirukkumaran, Don G Morris
Multiple Myeloma (MM), a clonal malignancy of antibody-producing plasma cells, is the second most common hematologic malignancy and results in significant patient morbidity and mortality. The high degree of immune dysregulation in MM, including T cell imbalances and up-regulation of immunosuppressive checkpoint proteins and myeloid derived suppressor cells, allows this malignancy to escape from host immune control. Despite advances in the therapeutic landscape of MM over the last decade, including the introduction of immunomodulatory drugs, the prognosis for this disease is poor, with less than 50% of patients surviving 5 years...
December 5, 2017: Blood Cancer Journal
https://www.readbyqxmd.com/read/29207960/decreased-expression-of-the-%C3%AE-2-integrin-on-tumor-cells-is-associated-with-a-reduction-in-liver-metastasis-of-colorectal-cancer-in-mice
#13
Aitor Benedicto, Joana Marquez, Alba Herrero, Elvira Olaso, Elzbieta Kolaczkowska, Beatriz Arteta
BACKGROUND: Lymphocyte Function-Associated Antigen-1 (LFA-1; CD18/CD11a) is one of the main adhesion molecules used by immune cells to infiltrate the liver under inflammatory conditions. Recently, the expression of this integrin has also been reported on several solid tumors, including colorectal cancer. However, its functional role in the metastatic progression to the liver remains unknown. Using in vitro assays and an experimental orthotopic in vivo model of liver metastasis, we aimed to elucidate the role of tumor LFA-1 in the metastatic progression by means of the partial depletion of the β2 subunit of LFA-1, required for integrin activation, firm adhesion and signaling...
December 6, 2017: BMC Cancer
https://www.readbyqxmd.com/read/29204699/therapeutic-reduction-of-cell-mediated-immunosuppression-in-mycosis-fungoides-and-s%C3%A3-zary-syndrome
#14
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/29204146/intracellular-s100a9-promotes-myeloid-derived-suppressor-cells-during-late-sepsis
#15
Jun Dai, Ajinkya Kumbhare, Dima Youssef, Charles E McCall, Mohamed El Gazzar
Myeloid precursor cell reprogramming into a myeloid-derived suppressor cell (MDSC) contributes to high mortality rates in mouse and human sepsis. S100A9 mRNA and intracellular protein levels increase during early sepsis and remain elevated in Gr1+CD11b+ MDSCs after pro-inflammatory sepsis transitions to the later chronic anti-inflammatory and immunosuppressive phenotype. The purpose of this study was to determine whether intracellular S100A9 protein might sustain Gr1+CD11b+ MDSC repressor cell reprogramming during sepsis...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29203668/epigenetic-therapy-activates-type-i-interferon-signaling-in-murine-ovarian-cancer-to-reduce-immunosuppression-and-tumor-burden
#16
Meredith L Stone, Katherine B Chiappinelli, Huili Li, Lauren M Murphy, Meghan E Travers, Michael J Topper, Dimitrios Mathios, Michael Lim, Ie-Ming Shih, Tian-Li Wang, Chien-Fu Hung, Vipul Bhargava, Karla R Wiehagen, Glenn S Cowley, Kurtis E Bachman, Reiner Strick, Pamela L Strissel, Stephen B Baylin, Cynthia A Zahnow
Ovarian cancer is the most lethal of all gynecological cancers, and there is an urgent unmet need to develop new therapies. Epithelial ovarian cancer (EOC) is characterized by an immune suppressive microenvironment, and response of ovarian cancers to immune therapies has thus far been disappointing. We now find, in a mouse model of EOC, that clinically relevant doses of DNA methyltransferase and histone deacetylase inhibitors (DNMTi and HDACi, respectively) reduce the immune suppressive microenvironment through type I IFN signaling and improve response to immune checkpoint therapy...
December 4, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29193231/using-mri-cell-tracking-to-monitor-immune-cell-recruitment-in-response-to-a-peptide-based-cancer-vaccine
#17
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/29190690/development-of-effective-tumor-immunotherapy-using-a-novel-dendritic-cell-targeting-toll-like-receptor-ligand
#18
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
#19
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
#20
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
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