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Myeloid-derived suppressor cells

Xuehua Chen, Yanfu Wang, Jiali Wang, Jinhui Wen, Xuzhao Jia, Xiaojun Wang, Hua Zhang
Chronic inflammation and immunosuppression lead to aging and tumorigenesis. T-helper 22 (Th22) cells, interleukin 22 (IL-22) and myeloid-derived suppressor cells (MDSCs) serve an important role in inflammatory-immune diseases and cancer. However, the status of Th22 cells, IL-22 and MDSCs in aging and elderly gastric cancer progression is unknown. In the present study, 39 elderly patients with gastric cancer (EGC), 32 elderly healthy controls (HE) and 31 young healthy controls (HY) were enrolled, and the peripheral Th22, Th17 and Th1 cells, and MDSCs, were examined using flow cytometry...
July 2018: Oncology Letters
Alessandra Sacchi, Nicola Tumino, Andrea Sabatini, Eleonora Cimini, Rita Casetti, Veronica Bordoni, Germana Grassi, Chiara Agrati
γδ T cells represent less than 5% of circulating T cells; they exert a potent cytotoxic function against tumor or infected cells and secrete cytokines like conventional αβ T cells. As αβ T cells γδ T cells reside in the typical T cell compartments (the lymph nodes and spleen), but are more widely distributed in tissues throughout the body. For these reasons, some investigators are exploring the possibility of immunotherapies aimed to expand and activate Vδ2 T cells, or using them as Chimeric Antigen Receptor carriers...
2018: Frontiers in Immunology
Karolina Okla, Iwona Wertel, Anna Wawruszak, Marcin Bobiński, Jan Kotarski
Progress in cancer treatment made by the beginning of the 21st century has shifted the paradigm from one-size-fits-all to tailor-made treatment. The popular vision, to study solid tumors through the relatively noninvasive sampling of blood, is one of the most thrilling and rapidly advancing fields in global cancer diagnostics. From this perspective, immune-cell analysis in cancer could play a pivotal role in oncology practice. This approach is driven both by rapid technological developments, including the analysis of circulating myeloid-derived suppressor cells (cMDSCs), and by the increasing application of (immune) therapies, the success or failure of which may depend on effective and timely measurements of relevant biomarkers...
June 21, 2018: Critical Reviews in Clinical Laboratory Sciences
Themis Alissafi, Aikaterini Hatzioannou, Konstantinos Mintzas, Roza Maria Barouni, Aggelos Banos, Sundary Sormendi, Alexandros Polyzos, Maria Xilouri, Ben Wielockx, Helen Gogas, Panayotis Verginis
Myeloid-derived suppressor cells (MDSCs) densely accumulate into tumors and potently suppress anti-tumor immune responses promoting tumor development. Targeting MDSCs in tumor immunotherapy has been hampered by lack of understanding of the molecular pathways that govern MDSC differentiation and function. Herein, we identify autophagy as a crucial pathway for MDSC-mediated suppression of anti-tumor immunity. Specifically, MDSCs in melanoma patients and mouse melanoma exhibited increased levels of functional autophagy...
June 19, 2018: Journal of Clinical Investigation
Fokhrul Hossain, Samarpan Majumder, Deniz A Ucar, Paulo C Rodriguez, Todd E Golde, Lisa M Minter, Barbara A Osborne, Lucio Miele
Cancer immunotherapy, which stimulates or augments host immune responses to treat malignancies, is the latest development in the rapidly advancing field of cancer immunology. The basic principles of immunotherapies are either to enhance the functions of specific components of the immune system or to neutralize immune-suppressive signals produced by cancer cells or tumor microenvironment cells. When successful, these approaches translate into long-term survival for patients. However, durable responses are only seen in a subset of patients and so far, only in some cancer types...
2018: Frontiers in Immunology
Stephan Lang, Kirsten Bruderek, Cordelia Kaspar, Benedikt Höing, Oliver Kanaan, Nina Dominas, Timon Hussain, Freya Droege, Christian Peter Eyth, Boris Hadaschik, Sven Brandau
PURPOSE: Myeloid-derived suppressor cells (MDSC) are a heterogeneous group of pathologically expanded myeloid cells with immunosuppressive activity. In human disease three major MDSC subpopulations can be defined as monocytic M-MDSC, granulocytic PMN-MDSC and early stage e-MDSC, which lack myeloid lineage markers of the former two subsets. It was the purpose of this study to determine and compare the immunosuppressive capacity and clinical relevance of each of these subsets in patients with solid cancer...
June 18, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Xinyu Tian, Jie Ma, Ting Wang, Jie Tian, Yu Zheng, Rongrong Peng, Yungang Wang, Yue Zhang, Lingxiang Mao, Huaxi Xu, Shengjun Wang
BACKGROUND: RUNX1 overlapping RNA (RUNXOR) is a long non-coding RNA that has been indicated as a key regulator in the development of myeloid cells by targeting runt-related transcription factor 1 (RUNX1). Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of cells consisting of immature granulocytes and monocytes with immunosuppression. However, the impact of lncRNA RUNXOR on the development of MDSCs remains unknown. METHODS: Both the expressions of RUNXOR and RUNX1 in the peripheral blood were measured by qRT-PCR...
June 18, 2018: BMC Cancer
Karthik M Kodigepalli, Serena Bonifati, Nagaraja Tirumuru, Li Wu
Sterile alpha motif and HD domain-containing protein 1 (SAMHD1) is a mammalian dNTP hydrolase that acts as a negative regulator in the efficacy of cytarabine treatment against acute myeloid leukemia (AML). However, the role of SAMHD1 in AML development and progression remains unknown. We have reported that SAMHD1 knockout (KO) in the AML-derived THP-1 cells results in enhanced proliferation and reduced apoptosis, but the underlying mechanisms are unclear. Here we show that SAMHD1 KO in THP-1 cells increased PI3K activity and reduced expression of the tumor suppressor PTEN...
June 18, 2018: Cell Cycle
Amanda Soares Alves, Mayari Eika Ishimura, Yeda Aparecida de Oliveira Duarte, Valquiria Bueno
Aim: The increased number of individuals older than 80 years, centenarians, and supercentenarians is not a synonym for healthy aging, since severe infections, hospitalization, and disability are frequently observed. In this context, a possible strategy is to preserve the main characteristics/functions of the immune system with the aim to cause less damage to the organism during the aging process. Vitamin D acts on bone marrow, brain, breast, malignant cells, and immune system and has been recommended as a supplement...
2018: Frontiers in Immunology
Xiaodong Guan, Zhiyu Liu, Jianhua Zhang, Xunbo Jin
BACKGROUND: Myeloid-derived suppressor cells (MDSC) play an important role in tumor-mediated immune evasion. Levels of MDSC in peripheral blood are increased in patients with cancer, correlating with cancer stage and outcome. Studies have confirmed the associations between MDSC and various cytokines in the peripheral blood of murine and human cancer hosts. However, little is known about the association between parenchymal MDSC subsets and cytokines, or the mechanism drawing MDSC into tumor parenchyma...
June 15, 2018: Advances in Clinical and Experimental Medicine: Official Organ Wroclaw Medical University
Weiyun Zhang, Jieting Huang, Min Wang, Dandan Song, Qiao Liao, Xia Rong, Tingting Li, Jean-Pierre Allain, Guangli Ren, Yongshui Fu, Chengyao Li
Myeloid-derived suppressor cells (MDSCs) accumulate from many diseases. MDSCs are rarely explored in occult hepatitis B virus infection (OBI). The frequency of M-MDSCs and G-MDSCs in OBI carriers was analyzed for correlation with clinical parameters, which was no different between OBI and healthy individuals, while the frequency of M-MDSCs but G-MDSCs in OBI was significantly lower than that observed in chronic hepatitis B (CHB) carriers (0.4% vs. 0.7%, P=0.0004). The frequency of MDSCs was not correlated with clinical parameters and viral load of OBI, suggesting that the absence of HBsAg in OBI carriers might not induce the accumulation of MDSCs...
June 13, 2018: Journal of Medical Virology
Mareike Grees, Adi Sharbi-Yunger, Christos Evangelou, Daniel Baumann, Gal Cafri, Esther Tzehoval, Stefan B Eichmüller, Rienk Offringa, Jochen Utikal, Lea Eisenbach, Viktor Umansky
Despite melanoma immunogenicity and remarkable therapeutic effects of negative immune checkpoint inhibitors, a significant fraction of patients does not respond to current treatments. This could be due to limitations in tumor immunogenicity and profound immunosuppression in the melanoma microenvironment. Moreover, insufficient tumor antigen processing and presentation by dendritic cells (DC) may hamper the development of tumor-specific T cells. Using two genetically engineered mouse melanoma models ( RET and BRAFV600E transgenic mice), in which checkpoint inhibitor therapy alone is not efficacious, we performed proof-of-concept studies with an improved, multivalent DC vaccination strategy based on our recently developed genetic mRNA cancer vaccines...
2018: Oncoimmunology
Guohui Qin, Jingyao Lian, Lan Huang, Qitai Zhao, Shasha Liu, Zhen Zhang, Xinfeng Chen, Dongli Yue, Lifeng Li, Feng Li, Lidong Wang, Viktor Umansky, Bin Zhang, Shengli Yang, Yi Zhang
Purpose : Tumor development has been closely linked to tumor microenvironment, particularly in terms of myeloid-derived suppressive cells (MDSCs), a heterogeneous population of immature myeloid cells that protect tumors from elimination by immune cells. Approaches aimed at blocking MDSC accumulation could improve cancer clinical outcome. Experimental Design : We investigated that metformin suppressed MDSC migration to inhibit cancer progression. Primary tumor tissues were incubated with metformin, and proinflammatory chemokine production was measured...
2018: Oncoimmunology
Laura Pinton, Samantha Solito, Elena Masetto, Marina Vettore, Stefania Canè, Alessandro Della Puppa, Susanna Mandruzzato
Meningiomas WHO grade I and II are common intracranial tumors in adults that normally display a benign outcome, but are characterized by a great clinical heterogeneity and frequent recurrence of the disease. Although the presence of an immune cell infiltrate has been documented in these tumors, a clear phenotypical and functional characterization of the immune web is missing. Here, we performed an extensive immunophenotyping of peripheral blood and fresh tumor tissue at surgery by multiparametric flow cytometry in 34 meningioma patients, along with immunosuppressive activity of sorted cells of myeloid origin...
2018: Oncoimmunology
Arnab Chattopadhyay, Xinying Yang, Pallavi Mukherjee, Dawoud Sulaiman, Hannah R Fogelman, Victor Grijalva, Steven Dubinett, Tonya C Wasler, Manash K Paul, Ramin Salehi-Rad, Julia J Mack, M Luisa Iruela-Arispe, Mohamad Navab, Alan M Fogelman, Srinivasa T Reddy
Having demonstrated that apolipoprotein A-I (apoA-I) mimetic peptides ameliorate cancer in mouse models, we sought to determine the mechanism for the anti-tumorigenic function of these peptides. CT-26 cells (colon cancer cells that implant and grow into tumors in the lungs) were injected into wild-type BALB/c mice. The day after injection, mice were either continued on chow or switched to chow containing 0.06% of a concentrate of transgenic tomatoes expressing the apoA-I mimetic peptide 6F (Tg6F). After four weeks, the number of lung tumors was significantly lower in Tg6F-fed mice...
June 13, 2018: Scientific Reports
Chukwunonso Onyilagha, Shiby Kuriakose, Nnamdi Ikeogu, Ping Jia, Jude Uzonna
Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of bone marrow-derived myeloid cells that have immune-suppressive activities. These cells have been reported to suppress T cell immunity against tumors as well as in some parasitic and bacterial infections. However, their role during Trypanosoma congolense infection has not been studied. Given that immunosuppression is a hallmark of African trypanosomiasis, we investigated the role of MDSCs in immunity to T. congolense infection. We found increased numbers of MDSCs in the spleen and liver of infected mice, which correlated with increased parasitemia...
June 13, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
Huoying Chen, Yao Chen, Hongbo Liu, Yi Que, Xing Zhang, Fang Zheng
Soft tissue sarcoma (STS) is a rare solid malignant cancer, and there are few effective treatment options for advanced disease. Cancer immunotherapy is a promising new strategy for STS treatment. IL-33 is a candidate cytokine for immunotherapy that can activate T lymphocytes and modulate antitumor immunity in some cancers. However, the expression and biological role of IL-33 in STS are poorly understood. In this study, we found that the expression of IL-33 and its receptor ST2 was decreased in STS using real-time PCR assays...
2018: Frontiers in Immunology
Antero Salminen, Kai Kaarniranta, Anu Kauppinen
Traditional herbal medicine has provided natural remedies against cancers and many age-related inflammatory diseases for thousands of years. Modern drug discovery techniques have revealed several active ingredients and their medicinal targets have been characterized. Concurrently, there has been great progress in understanding the pathological mechanisms underpinning cancers and inflammatory diseases. These studies have demonstrated that immature myeloid-derived suppressor cells (MDSCs) have a crucial role in the immune escape of cancer cells thus promoting tumor growth...
June 8, 2018: International Immunopharmacology
Yue Wang, Xiaokai Zhang, Liangliang Yang, Jinru Xue, Guangrui Hu
Myeloid derived suppressor cells (MDSC) play a pivotal role in tumor immune evasion and MDSC levels increased in patients with cancer. Studies confirmed the associations between MDSC and various cytokines in the peripheral blood. However, little is known about the association between parenchymal MDSC subsets and cytokines, or the mechanism drawing MDSC into tumor parenchyma. This study was to analyze the correlation between MDSC subsets and CCL2 level in lung cancer model. G-MDSC and M-MDSC from the blood and parenchyma were analyzed by flow cytometry and western blot in the lung tumor model...
June 2018: Journal of Bone Oncology
Yuqiao Sheng, Feng Li, Zhihai Qin
Tumor necrosis factor (TNF) is widely accepted as a tumor-suppressive cytokine via its ubiquitous receptor TNF receptor 1 (TNFR1). The other receptor, TNFR2, is not only expressed on some tumor cells but also on suppressive immune cells, including regulatory T cells and myeloid-derived suppressor cells. In contrast to TNFR1, TNFR2 diverts the tumor-inhibiting TNF into a tumor-advocating factor. TNFR2 directly promotes the proliferation of some kinds of tumor cells. Also activating immunosuppressive cells, it supports immune escape and tumor development...
2018: Frontiers in Immunology
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