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Cho-Rong Lee, Wongeun Lee, Steve K Cho, Sung-Gyoo Park
Myeloid-derived suppressor cells (MDSCs) regulate T cell immunity, and this population is a new therapeutic target for immune regulation. A previous study showed that transforming growth factor-β (TGF-β) is involved in controlling MDSC differentiation and immunoregulatory function in vivo. However, the direct effect of TGF-β on MDSCs with various cytokines has not previously been tested. Thus, we examined the effect of various cytokine combinations with TGF-β on MDSCs derived from bone marrow cells. The data show that different cytokine combinations affect the differentiation and immunosuppressive functions of MDSCs in different ways...
March 15, 2018: International Journal of Molecular Sciences
Sagus Sampath, Haejung Won, Erminia Massarelli, Min Li, Paul Frankel, Nayana Vora, Lalit Vora, Ellie Maghami, Marcin Kortylewski
Immunomodulation contributes to the antitumor efficacy of the fractionated radiation therapy (RT). Here, we describe immune effects of RT with concurrent systemic cisplatin or cetuximab treatment of patients with stage III-IV head and neck squamous cell carcinoma (HNSCC). Using longitudinally collected blood samples, we identified significant changes in cytokines/chemokines and immune cell populations compared to immune-related gene expression profiles in peripheral blood mononuclear cells (PBMCs). The 7-week combinatorial RT resulted in gradual elevation of proinflammatory mediators (IFNγ, IL-6, TNFɑ, CCL2), while levels of IL-12, cytokine essential for antitumor immune responses, were decreased...
February 16, 2018: Oncotarget
Takuya Tsubaki, Tetsuya Kadonosono, Shimon Sakurai, Tadashi Shiozawa, Toshiki Goto, Shiori Sakai, Takahiro Kuchimaru, Takeharu Sakamoto, Hitomi Watanabe, Gen Kondoh, Shinae Kizaka-Kondoh
The immunosuppressive tumor microenvironment is a hallmark of cancer. Myeloid-derived suppressor cells (MDSCs) are CD11b+ Gr-1+ tumor-infiltrating immature myeloid cells that strongly mediate tumor immunosuppression. The CD11b+ Gr-1+ cells are a heterogeneous cell population, and the impacts of each subpopulation on tumor progression are not yet completely understood. In the present study, we identified a novel subpopulation of CD11b+ Gr-1+ cells from murine lung carcinoma tumors according to their strongly adherent abilities...
February 16, 2018: Oncotarget
Wensheng Zhang, Wanzhuo He, Xiaodong Shi, Xiao Li, Yuanyuan Wang, Minghua Hu, Fangli Ma, Ning Tao, Guiqin Wang, Zhihai Qin
Despite decades of research, malignant tumors are extremely difficult to eliminate with conventional methods. Although surgical resection potentially eradicates the problem, only a few cases are suitable for operation, and other approaches often involve harmful consequences. Revolutionary methods are desperately needed to improve patient outcomes and diminish harmful side effects. Myeloid-derived suppressor cells (MDSCs), downregulators of the innate and adaptive immune systems, have been widely studied over the past 2 decades...
March 13, 2018: Phytotherapy Research: PTR
Mirhane Hassan, Hala M Raslan, Hesham Gamal Eldin, Eman Mahmoud, Hanaa Alm-Elhuda Abd Elwajed
INTRODUCTION: Type 1 Diabetes Mellitus (T1D) is an autoimmune disease that results from the destruction of insulin-producing beta cells of the pancreas by autoreactive T cells. Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of cells that can potently suppress T cell responses. AIM: To detect the presence of MDSCs in T1D and compare their percentage in T1D versus healthy individuals. METHOD: Thirty T1D patients were included in the study...
February 15, 2018: Open Access Macedonian Journal of Medical Sciences
Yunhuan Gao, Tiantian Wang, Yuanyuan Li, Yuan Zhang, Rongcun Yang
Myeloid-derived suppressor cells (MDSCs) are major regulators of immune responses in cancer. Both C/EBP homologous protein (CHOP) and C/EBPβ play a critical role in regulating immunosuppressive function of MDSCs. In this study, we identified a novel long noncoding RNA termed as lnc-chop in MDSCs, which may interact with CHOP and the C/EBPβ isoform liver-enriched inhibitory protein. The binding of lnc-chop with both CHOP and the C/EBPβ isoform liver-enriched inhibitory protein promoted the activation of C/EBPβ and upregulated the expression of arginase-1, NO synthase 2, NADPH oxidase 2, and cyclooxygenase-2, which are related to the immunosuppressive function of MDSCs in inflammatory and tumor environments...
March 12, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
Mario P Colombo, Elena Jachetti, Valeria Cancila, Alice Rigoni, Lucia Bongiovanni, Barbara Cappetti, Beatrice Belmonte, Claudia Enriquez, Patrizia Casalini, Paola Ostano, Barbara Frossi, Sabina Sangaletti, Claudia Chiodoni, Giovanna Chiorino, Carlo E Pucillo, Claudio Tripodo
Immunotherapy, including the use of checkpoint inhibitors, is a potent therapeutic approach for some cancers, but has limited success with prostate tumors, in which immune suppression is instigated by the tumor. The immunosuppressive capacity of mast cells, which promote adenocarcinoma development in the prostate, prompted our investigation on whether mast cells promote tolerance to SV40 Large-T antigen, the transforming oncogene in transgenic adenocarcinoma of the mouse prostate (TRAMP) mice. The incidence of adenocarcinoma was reduced in the offspring of a cross between TRAMP mice and mast cell-deficient KitWsh mice...
March 9, 2018: Cancer Immunology Research
Tao Wang, Yuanyuan Wen, Xiaochong Fan
CD4+ T cells play an important role in the progression of type 2 diabetes mellitus (T2DM). It is known that T cell responses can be suppressed by myeloid-derived suppressor cells (MDSCs). In this study, we aimed to explore the potential role of MDSCs in the progression of T2DM, and to examine whether the underlying mechanism was associated with CD4+ T cells. Peripheral blood samples were obtained from T2DM patients and healthy controls, as well as C57BL6J db/db mice and control heterozygous (db/-) mice. The frequency of MDSCs and CD4+ T cells was analyzed using flow cytometry...
March 5, 2018: Acta Biochimica et Biophysica Sinica
Najmeh Khosravianfar, Jamshid Hadjati, Afshin Namdar, Roobina Boghozian, Morteza Hafezi, Mahboubeh Ashourpour, Nasim Kheshtchin, Mahsa Banitalebi, Reza Mirzaei, Seyed Alireza Razavi
Myeloid-derived suppressor cells (MDSCs) are capable of suppressing the immune response. 5-Fluorouracil (5-FU) compared to other chemotherapy drugs have shown considerable decreases in the number of MDSCs without visible effects on T, B and natural killer cells, as well as dendritic cells (DCs). DC-based vaccines considered to be appropriate candidates for cancer immunotherapy. However, due to the presence of various factors like MDSCs in tumor microenvironment, DC vaccine cannot effectively perform its function...
February 2018: Iranian Journal of Allergy, Asthma, and Immunology
Shinji Okano, Kareem Abu-Elmagd, Danielle D Kish, Karen Keslar, William M Baldwin, Robert L Fairchild, Masato Fujiki, Ajai Khanna, Mohammed Osman, Guilherme Costa, John Fung, Charles Miller, Hiroto Kayashima, Koji Hashimoto
Recent advances in immunosuppressive regimens have decreased acute cellular rejection (ACR) rates and improved intestinal transplant (ITx) recipient survival. We investigated the role of myeloid-derived suppressor cells (MDSCs) in ITx. We identified MDSCs as CD33+ CD11b+ lineage(CD3/CD56/CD19)- HLA-DR-/low cells with 3 subsets, CD14- CD15- (e-MDSC), CD14+ CD15- (M-MDSC), and CD14- CD15+ (PMN-MDSC), in peripheral blood mononuclear cells (PBMCs) and mononuclear cells in the grafted intestinal mucosa. Total MDSC numbers increased in PBMCs following ITx; among MDSC subsets, M-MDSC numbers were maintained at high level after 2 months following ITx...
March 6, 2018: American Journal of Transplantation
Katarzyna C Pituch, Jason Miska, Giedre Krenciute, Wojciech K Panek, Gina Li, Tania Rodriguez-Cruz, Meijing Wu, Yu Han, Maciej S Lesniak, Stephen Gottschalk, Irina V Balyasnikova
In order to fully harness the potential of immunotherapy with chimeric antigen receptor (CAR)-modified T cells, pre-clinical studies must be conducted in immunocompetent animal models that closely mimic the immunosuppressive malignant glioma (MG) microenvironment. Thus, the goal of this project was to study the in vivo fate of T cells expressing CARs specific for the MG antigen IL13Rα2 (IL13Rα2-CARs) in immunocompetent MG models. Murine T cells expressing IL13Rα2-CARs with a CD28.ζ (IL13Rα2-CAR.CD28...
February 8, 2018: Molecular Therapy: the Journal of the American Society of Gene Therapy
Xia Shao, Boting Wu, Luya Cheng, Feng Li, Yanxia Zhan, Chanjuan Liu, Lili Ji, Zhihui Min, Yang Ke, Lihua Sun, Hao Chen, Yunfeng Cheng
BACKGROUND: Although impaired myeloid-derived suppressor cells (MDSCs) recently have been studied in immune thrombocytopenia (ITP), another myeloid-derived cell population signified as M2 macrophages has not been investigated properly in ITP patients. In the present study, we intended to determine the features of circulating M2-like macrophages, to examine its relationship with MDSCs, and to explore their prognostic values in ITP. METHODS: Peripheral blood mononuclear cells from healthy controls and primary ITP patients were isolated to test the circulating M2-like macrophages and MDSCs...
March 2, 2018: Journal of Translational Medicine
Yang Zhao, Xiao-Fei Shen, Ke Cao, Jie Ding, Xing Kang, Wen-Xian Guan, Yi-Tao Ding, Bao-Rui Liu, Jun-Feng Du
How to induce immune tolerance without long-term need for immunosuppressive drugs has always been a central problem in solid organ transplantation. Modulating immunoregulatory cells represents a potential target to resolve this problem. Myeloid-derived suppressor cells (MDSCs) are novel key immunoregulatory cells in the context of tumor development or transplantation, and can be generated in vitro . However, none of current systems for in vitro differentiation of MDSCs have successfully achieved long-term immune tolerance...
2018: Frontiers in Immunology
Min-Jung Park, Sung-Hee Lee, Eun-Kyung Kim, Eun-Jung Lee, Jin-Ah Baek, Sung-Hwan Park, Seung-Ki Kwok, Mi-La Cho
Myeloid-derived suppressor cells (MDSCs) are heterogenous populations of immature myeloid progenitor cells with immunoregulatory function. MDSCs play critical roles in controlling the processes of autoimmunity but their roles in rheumatoid arthritis (RA) are controversial. The present study was undertaken to investigate whether MDSCs have therapeutic impact in mice with collagen-induced arthritis (CIA), an animal model of RA. We also examined the mechanisms underlying the anti-arthritic effect of MDSCs. In vitro treatment with MDSCs repressed IL-17 but increased FOXP3 in CD4+ T cells in mice...
February 28, 2018: Scientific Reports
Miriam Mecha, Ana Feliú, Isabel Machín, Cesar Cordero, Francisco Carrillo-Salinas, Leyre Mestre, Gloria Hernández-Torres, Silvia Ortega-Gutiérrez, María L López-Rodríguez, Fernando de Castro, Diego Clemente, Carmen Guaza
The innate immune response is mediated by primary immune modulators such as cytokines and chemokines that together with immune cells and resident glia orchestrate CNS immunity and inflammation. Growing evidence supports that the endocannabinoid 2-arachidonoylglycerol (2-AG) exerts protective actions in CNS injury models. Here, we used the acute phase of Theiler's virus induced demyelination disease (TMEV-IDD) as a model of acute neuroinflammation to investigate whether 2-AG modifies the brain innate immune responses to TMEV and CNS leukocyte trafficking...
February 27, 2018: Glia
Po-Hao Feng, Chih-Teng Yu, Kuan-Yuan Chen, Ching-Shan Luo, Shen Ming Wu, Chien-Ying Liu, Lu Wei Kuo, Yao-Fei Chan, Tzu-Tao Chen, Chih-Cheng Chang, Chun-Nin Lee, Hsiao-Chi Chuang, Chiou-Feng Lin, Chia-Li Han, Wei-Hwa Lee, Kang-Yun Lee
Background: Monocytic myeloid-derived suppressor cells (MDSCs), particularly the S100A9+ subset, has been shown initial clinical relevance. However, its role in EGFR-mutated lung adenocarcinoma, especially to EGFR-tyrosine kinase inhibitor (EGFR-TKI) is not clear. In a clinical setting of EGFR mutated lung adenocarcinoma, a role of the MDSC apart from T cell suppression was also investigated. Results: Blood monocytic S100A9+ MDSC counts were higher in lung cancer patients than healthy donors, and were associated with poor treatment response and shorter progression-free survival (PFS)...
January 26, 2018: Oncotarget
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
Nicole Janssen, Lisa Speigl, Graham Pawelec, Heike Niessner, Christopher Shipp
Metastatic melanoma is the most dangerous form of skin cancer, with an ever-increasing incidence worldwide. Despite encouraging results with immunotherapeutic approaches, long-term survival is still poor. This is likely partly due to tumour-induced immune suppression mediated by myeloid-derived suppressor cells (MDSCs), which were shown to be associated with response to therapy and survival. Thus, identifying pathways responsible for MDSC differentiation may provide new therapeutic targets and improve efficacy of existing immunotherapies...
February 21, 2018: Cellular Immunology
Yihang Jiang, Sujuan Feng, Jiawei Ji, Zhemin Lin, Xiaodong Zhang
INTRODUCTION: Post-infectious immunosuppression is disadvantageous to patients' long-term outcomes, especially in transplant recipients receiving large doses of immunosuppressants. A growing body of evidence indicates the immunoregulatory ability of myeloid-derived suppressor cells (MDSCs). We herein investigate the characteristics of monocytic-MDSCs (M-MDSCs) in a cohort of renal transplant recipients with/without infection to clarify the potential involvement in post-infectious immunosuppression...
February 22, 2018: Transplant Immunology
Upasana Kulkarni, Christoph Herrmenau, Stephanie J Win, Michael Bauer, Thomas Kamradt
Immunological dysregulation in sepsis is associated with often lethal secondary infections. Loss of effector cells and an expansion of immunoregulatory cell populations both contribute to sepsis-induced immunosuppression. The extent and duration of this immunosuppression are unknown. Interleukin 7 (IL-7) is important for the maintenance of lymphocytes and can accelerate the reconstitution of effector lymphocytes in sepsis. How IL-7 influences immunosuppressive cell populations is unknown. We have used the mouse model of peritoneal contamination and infection (PCI) to investigate the expansion of immunoregulatory cells as long-term sequelae of sepsis with or without IL-7 treatment...
2018: PloS One
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