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Myeloid derived suppressor cell

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https://www.readbyqxmd.com/read/28433543/phenformin-inhibits-myeloid-derived-suppressor-cells-and-enhances-the-anti-tumor-activity-of-pd-1-blockade-in-melanoma
#1
Sun Hye Kim, Man Li, Sebastian Trousil, Yaqing Zhang, Marina Pasca di Magliano, Kenneth D Swanson, Bin Zheng
Biguanides, such as the diabetes therapeutics metformin and phenformin, have demonstrated antitumor activity both in vitro and in vivo. However, their potential effects on the tumor microenvironment are largely unknown. Here we report that phenformin selectively inhibits granulocytic myeloid-derived suppressor cells (G-MDSCs) in spleens of tumor bearing mice and ex vivo. Phenformin induces production of reactive oxygen species in G-MDSC, whereas the antioxidant N-acetylcysteine attenuates the inhibitory effects of phenformin...
April 19, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/28427434/adenovirus-mediated-cd40l-gene-transfer-increases-teffector-tregulatory-cell-ratio-and-upregulates-death-receptors-in-metastatic-melanoma-patients
#2
A Schiza, J Wenthe, S Mangsbo, E Eriksson, Anders Nilsson, T H Tötterman, A Loskog, G Ullenhag
BACKGROUND AND AIMS: Malignant melanoma is an aggressive tumor sensitive for immunotherapy such as checkpoint blockade antibodies. Still, most patients with late stage disease do not respond, and the side effects can be severe. Stimulation of the CD40 pathway to initiate anti-tumor immunity is a promising alternative. Herein, we demonstrate immune profiling data from melanoma patients treated with an adenovirus-based CD40 ligand gene therapy (AdCD40L). METHODS: Peripheral blood mononuclear cells and plasma were collected from malignant melanoma patients (n = 15) enrolled in a phase I/IIa study investigating intratumoral delivery of AdCD40L with or without low dose cyclophosphamide...
April 20, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28426268/putative-biomarkers-of-response-to-treatment-in-breast-cancer-patients-a-pilot-assay
#3
María J Rico, Herman A Perroud, Cintia Herrera, Carlos M Alasino, Eduardo A Roggero, Stella M Pezzotto, Ana Lía Nocito, Viviana R Rozados, O Graciela Scharovsky
Identifying tumor biomarkers associated with clinical behavior in breast cancer patients may allow higher accuracy in the selection of treatment. Different types of cells were determined in the primary tumors of stage I, II, and III of breast cancer patients, who were assigned to one of the two groups: (1) disease-free or (2) relapsed/progressed, at 5 years after primary treatment. We studied 32 tumor samples. CD4(+) lymphocytes and CD44(+)CD24(-/low) cells (cancer stem cells) showed a significant association with clinical outcome at 5 years of primary treatment, while CD8(+), Foxp3(+), CD34(+), and myeloid-derived suppressor cells did not show any association...
April 20, 2017: Cancer Investigation
https://www.readbyqxmd.com/read/28423487/ipilimumab-treatment-decreases-monocytic-mdscs-and-increases-cd8-effector-memory-t-cells-in-long-term-survivors-with-advanced-melanoma
#4
Yago Pico de Coaña, Maria Wolodarski, Isabel Poschke, Yuya Yoshimoto, Yuan Yang, Maria Nyström, Ulrika Edbäck, Suzanne Eghyazi Brage, Andreas Lundqvist, Giuseppe V Masucci, Johan Hansson, Rolf Kiessling
Ipilimumab has revolutionized malignant melanoma therapy, but a better understanding of the mechanisms behind treatment response and adverse effects is needed. In this work, the immune system of ipilimumab treated patients was monitored to investigate potential mechanisms of action that may correlate with treatment outcome. Blood samples from 43 advanced melanoma patients were taken before, during and at the end of treatment. Hematological parameters were measured and flow cytometry analysis was performed in fresh samples within two hours of sample collection...
March 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28421069/engineering-chimeric-antigen-receptor-t-cells-for-racing-in-solid-tumors-don-t-forget-the-fuel
#5
REVIEW
Melita Irving, Romain Vuillefroy de Silly, Kirsten Scholten, Nahzli Dilek, George Coukos
T-cells play a critical role in tumor immunity. Indeed, the presence of tumor-infiltrating lymphocytes is a predictor of favorable patient prognosis for many indications and is a requirement for responsiveness to immune checkpoint blockade therapy targeting programmed cell death 1. For tumors lacking immune infiltrate, or for which antigen processing and/or presentation has been downregulated, a promising immunotherapeutic approach is chimeric antigen receptor (CAR) T-cell therapy. CARs are hybrid receptors that link the tumor antigen specificity and affinity of an antibody-derived single-chain variable fragment with signaling endodomains associated with T-cell activation...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28418921/c-ebp-%C3%AE-positively-regulates-mdsc-expansion-and-endothelial-vegfr2-expression-in-tumor-development
#6
Yongfen Min, Jingdong Li, Peng Qu, P Charles Lin
Vascular endothelial cells and Gr-1+CD11b+ myeloid derived suppressor cells (MDSCs) are two important components that constitute the tumor microenvironment. Targeting these cells offers the potential to halt tumor growth. In this study, we report a common mediator in C/EBP-δ that regulates both components and aids in tumor development. C/EBP-δ is elevated in tumor derived MDSCs. Interestingly, genetic deletion of C/EBP-δ in mice significantly impaired MDSC expansion in response to tumor progression, but it had no effect on Gr-1+CD11b+ cell production in normal development...
March 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/28418913/accumulation-of-myeloid-derived-suppressor-cells-mdscs-induced-by-low-levels-of-il-6-correlates-with-poor-prognosis-in-bladder-cancer
#7
Guoliang Yang, Wenyan Shen, Yan Zhang, Mengyao Liu, Lianhua Zhang, Qiang Liu, Hui Hui Lu, Juanjie Bo
Bladder cancer (BC) is one of the most commonly occurring cancers, with a high recurrence rate and poor outcomes in cases of relapsed metastatic disease. Here, we analyzed the markers and significance of myeloid-derived suppressor cells (MDSCs) for BC development and progression. MDSC markers were examined in peripheral blood from 113 BC patients and 20 healthy volunteers. We identified CD11b+CD33lowHLA-DR- CD3- cells as markers of MDSCs in peripheral blood from BC patients. We also demonstrated that MDSC numbers are higher in BC patients than healthy donors, and that MDSC numbers correlate with the clinical grade, stage, and poor prognosis...
March 20, 2017: Oncotarget
https://www.readbyqxmd.com/read/28417112/lectin-type-oxidized-ldl-receptor-1-distinguishes-population-of-human-polymorphonuclear-myeloid-derived-suppressor-cells-in-cancer-patients
#8
Thomas Condamine, George A Dominguez, Je-In Youn, Andrew V Kossenkov, Sridevi Mony, Kevin Alicea-Torres, Evgenii Tcyganov, Ayumi Hashimoto, Yulia Nefedova, Cindy Lin, Simona Partlova, Alfred Garfall, Dan T Vogl, Xiaowei Xu, Stella C Knight, George Malietzis, Gui Han Lee, Evgeniy Eruslanov, Steven M Albelda, Xianwei Wang, Jawahar L Mehta, Meenakshi Bewtra, Anil Rustgi, Neil Hockstein, Robert Witt, Gregory Masters, Brian Nam, Denis Smirnov, Manuel A Sepulveda, Dmitry I Gabrilovich
Polymorphonuclear myeloid-derived suppressor cells (PMN-MDSC) are important regulators of immune responses in cancer and have been directly implicated in promotion of tumor progression. However, the heterogeneity of these cells and lack of distinct markers hampers the progress in understanding of the biology and clinical importance of these cells. Using partial enrichment of PMN-MDSC with gradient centrifugation we determined that low density PMN-MDSC and high density neutrophils from the same cancer patients had a distinct gene profile...
August 2016: Science Immunology
https://www.readbyqxmd.com/read/28416485/targeting-autocrine-ccl5-ccr5-axis-reprograms-immunosuppressive-myeloid-cells-and-reinvigorates-antitumor-immunity
#9
Yi Ban, Junhua Mai, Xin Li, Marisa Mitchell-Flack, Tuo Zhang, Lixing Zhang, Lotfi Chouchane, Mauro Ferrari, Haifa Shen, Xiaojing Ma
The tumor-promoting potential of CCL5 has been proposed but remains poorly understood. We demonstrate here that an autocrine CCL5-CCR5 axis is a major regulator of immunosuppressive myeloid cells (IMC) of both monocytic and granulocytic lineages. The absence of the autocrine CCL5 abrogated the generation of granulocytic myeloid-derived suppressor cells and tumor-associated macrophages. In parallel, enhanced maturation of intratumoral neutrophils and macrophages occurred in spite of tumor-derived CCL5. The refractory nature of ccl5-null myeloid precursors to tumor-derived CCL5 was attributable to their persistent lack of membrane-bound CCR5...
April 17, 2017: Cancer Research
https://www.readbyqxmd.com/read/28415797/rab7-gtpase-controls-lipid-metabolic-signaling-in-myeloid-derived-suppressor-cells
#10
Xinchun Ding, Wenjing Zhang, Ting Zhao, Cong Yan, Hong Du
Lysosomal acid lipase (LAL) is a critical neutral lipid metabolic enzyme that regulates metabolic reprogramming in myeloid-derived suppressor cells (MDSCs) through over-activation of mammalian target of rapamycin (mTOR). Affymetrix GeneChip microarray analysis of MDSCs from LAL deficient mouse (lal-/-) revealed upregulation of Rab7 GTPase protein, which belongs to a superfamily of small-molecular-weight GTPase known to regulate intracellular membrane trafficking from early to late endosomes and lysosomes. Here, the physical protein-protein interaction between Rab7 GTPase and mTOR has been detected by co-immunoprecipitation in the cell extract of wild type HD1A and lal-/- MDSC-like HD1B myeloid cell lines...
March 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28414726/neem-leaf-glycoprotein-prevents-post-surgical-sarcoma-recurrence-in-swiss-mice-by-differentially-regulating-cytotoxic-t-and-myeloid-derived-suppressor-cells
#11
Madhurima Sarkar, Sarbari Ghosh, Avishek Bhuniya, Tithi Ghosh, Ipsita Guha, Subhasis Barik, Jaydip Biswas, Anamika Bose, Rathindranath Baral
Post-surgical tumor recurrence is a common problem in cancer treatment. In the present study, the role of neem leaf glycoprotein (NLGP), a novel immunomodulator, in prevention of post-surgical recurrence of solid sarcoma was examined. Data suggest that NLGP prevents tumor recurrence after surgical removal of sarcoma in Swiss mice and increases their tumor-free survival time. In NLGP-treated tumor-free mice, increased cytotoxic CD8+ T cells and a decreased population of suppressor cells, especially myeloid-derived suppressor cells (MDSCs) was observed...
2017: PloS One
https://www.readbyqxmd.com/read/28412745/neutrophil-count-is-associated-with-myeloid-derived-suppressor-cell-level-and-presents-prognostic-value-of-for-hepatocellular-carcinoma-patients
#12
Xing Li, Yan-Fang Xing, Ai-Hua Lei, Qiang Xiao, Zhi-Huan Lin, Ying-Fen Hong, Xiang-Yuan Wu, Jie Zhou
Myeloid Derived Suppressor Cell (MDSC) has been raised to be a novel target for multiple cancers. However, target agents on MDSC have not display promising efficacy. One of the critical reasons shall be less optimal patient selection. In the present study, we aimed to identify clinical parameters relevant to MDSC level in hepatocellular carcinoma (HCC) patients for future MDSC targeted therapy. In the present study, a series of 55 HCC patients (testing group) and 20 healthy donors were analyzed investigating frequencies of MDSC in peripheral blood mononuclear cells (PBMC)...
February 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/28411578/differential-effects-of-low-dose-fludarabine-or-5-fluorouracil-on-the-tumor-growth-and-myeloid-derived-immunosuppression-status-of-tumor-bearing-mice
#13
Manuchehr Abedi-Valugerdi, Wenyi Zheng, Fadwa Benkessou, Ying Zhao, Moustapha Hassan
Myeloid-derived suppressor cells (MDSCs) accumulate in tumor-bearing hosts and play a key role in the suppression of the innate and adaptive immunity. Chemotherapeutic strategies have been developed to deplete or deactivate MDSCs in different tumor models. The pyrimidine analog, 5-fluorouracil (5-FU) is found to reduce the tumor size by depleting MDSCs. Here, we asked whether the purine analog, fludarabine (Flu), could exert similar effects. Employing a lymphoma model, we demonstrated that in mice with advanced tumors (where MDSC-induced suppression was present), treatment with a single low-dose Flu (25, 50, 100mg/kg) elevated the numbers of splenic MDSCs and serum arginase activity, and simultaneously, increased the tumor growth (only the highest dose)...
April 12, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28407569/expansion-of-monocytic-myeloid-derived-suppressor-cells-in-endometriosis-patients-a-pilot-study
#14
Haiwen Chen, Shuang Qin, Aihua Lei, Xing Li, Qi Gao, Jingyin Dong, Qing Xiao, Jie Zhou
Endometriosis is a chronic inflammation disease and is closely associated with immune dysregulation. Myeloid-derived suppressor cells (MDSCs) are a negative regulator of the immune system. The aim of this study was to evaluate the possible role of MDSCs in endometriosis patients. We collected the peripheral blood and peritoneal fluid from endometriosis patients and controls and analyzed M-MDSCs level using specific monoclonal antibodies recognizing HLA-DR, CD33, CD11b, CD14 markers by flow cytometry. We found that there existed abnormal expansion of monocytic MDSCs (M-MDSCs) (HLA-DR(-/low)CD33(+)CD11b(+) CD14(+)) in peripheral blood and peritoneal fluid of patients with endometriosis...
April 10, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28405677/metastasized-murine-oral-squamous-cell-carcinoma-cells-induce-intratumoral-polymorphonuclear-myeloid-derived-suppressor-cells
#15
Shigeki Sumi, Naoki Umemura, Eiji Takayama, Emika Ohkoshi, Makoto Adachi, Masako Mizuno-Kamiya, Toshihiro Inagaki, Harumi Kawaki, Shinichiro Sumitomo, Nobuo Kondoh
Myeloid derived suppressor cells (MDSCs) localize to hematopoietic organs and peripheral blood during inflammation or tumor tissues and lymph nodes in the presence of a tumor. However, whether there are differences in MDSCs found in the primary tumor and metastases is unknown. In the present study, we established a cell line of metastasized tumor cells to a lymph node, L5-11, which were derived from the Sq-1979 mouse buccal mucosa squamous cell carcinoma cell line. We then analyzed tumor immunogenicity, especially with regard to MDSCs, to clarify the differences between the primary tumor and metastases, using an isogenic heterotopic tumor transplantation model...
May 2017: Oncology Reports
https://www.readbyqxmd.com/read/28405502/il4-induced-gene-1-promotes-tumor-growth-by-shaping-the-immune-microenvironment-in-melanoma
#16
Lloyd Bod, Renée Lengagne, Ludovic Wrobel, Jan Philipp Ramspott, Masashi Kato, Marie-Françoise Avril, Flavia Castellano, Valérie Molinier-Frenkel, Armelle Prévost-Blondel
Amino acid catabolizing enzymes emerged as a crucial mechanism used by tumors to dampen immune responses. The L-phenylalanine oxidase IL-4 induced gene 1 (IL4I1) is expressed by tumor-associated myeloid cells of most solid tumors, including melanoma. We previously provided the only evidence that IL4I1 accelerates tumor growth by limiting the CD8(+) T cell mediated immune response, in a mouse model of melanoma cell transplantation. Here, we explored the role of IL4I1 in Ret mice, a spontaneous model of melanoma...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28405495/biological-and-clinical-significance-of-tryptophan-catabolizing-enzymes-in-cutaneous-t-cell-lymphomas
#17
Pilvi Maliniemi, Kirsi Laukkanen, Liisa Väkevä, Katja Dettmer, Tuomas Lipsanen, Leila Jeskanen, Alban Bessede, Peter J Oefner, Marshall E Kadin, Annamari Ranki
Indoleamine 2,3-deoxygenase 1 (IDO1) induces immune tolerance in the tumor microenvironment (TME) and is recognized as a potential therapeutic target. We studied the expression of both IDO1 and the related tryptophan 2,3-dioxygenase (TDO) in several different subtypes of cutaneous T-cell lymphoma (CTCL), and evaluated the kynurenine (KYN) pathway in the local TME and in patient sera. Specimens from the total of 90 CTCL patients, including mycosis fungoides (MF, n = 37), lymphomatoid papulosis (LyP, n = 36), primary cutaneous anaplastic large cell lymphoma (pcALCL, n = 4), subcutaneous panniculitis-like T-cell lymphoma (SPTCL n = 13), and 10 patients with inflammatory lichen ruber planus (LRP), were analyzed by immunohistochemistry (IHC), immunofluorescence (IF), quantitative PCR, and/or liquid chromatography-tandem mass spectrometry (LC-MS/MS)...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28401653/selective-blockade-of-b7-h3-enhances-antitumour-immune-activity-by-reducing-immature-myeloid-cells-in-head-and-neck-squamous-cell-carcinoma
#18
Liang Mao, Teng-Fei Fan, Lei Wu, Guang-Tao Yu, Wei-Wei Deng, Lei Chen, Lin-Lin Bu, Si-Rui Ma, Bing Liu, Yansong Bian, Ashok B Kulkarni, Wen-Feng Zhang, Zhi-Jun Sun
Immature myeloid cells including myeloid-derived suppressor cells (MDSCs) and tumour-associated macrophages (TAMs) promote tumour growth and metastasis by facilitating tumour transformation and angiogenesis, as well as by suppressing antitumour effector immune responses. Therefore, strategies designed to reduce MDSCs and TAMs accumulation and their activities are potentially valuable therapeutic goals. In this study, we show that negative immune checkpoint molecule B7-H3 is significantly overexpressed in human head and neck squamous cell carcinoma (HNSCC) specimen as compared with normal oral mucosa...
April 11, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28401258/tumor-associated-myeloid-cells-as-guiding-forces-of-cancer-cell-stemness
#19
REVIEW
Antonio Sica, Chiara Porta, Alberto Amadori, Anna Pastò
Due to their ability to differentiate into various cell types and to support tissue regeneration, stem cells simultaneously became the holy grail of regenerative medicine and the evil obstacle in cancer therapy. Several studies have investigated niche-related conditions that favor stemness properties and increasingly emphasized their association with an inflammatory environment. Tumor-associated macrophages (TAMs) and myeloid-derived suppressor cells (MDSCs) are major orchestrators of cancer-related inflammation, able to dynamically express different polarized inflammatory programs that promote tumor outgrowth, including tumor angiogenesis, immunosuppression, tissue remodeling and metastasis formation...
April 11, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28400539/mass-cytometry-deep-phenotyping-of-human-mononuclear-phagocytes-and-myeloid-derived-suppressor-cells-from-human-blood-and-bone-marrow
#20
Mikael Roussel, P Brent Ferrell, Allison R Greenplate, Faustine Lhomme, Simon Le Gallou, Kirsten E Diggins, Douglas B Johnson, Jonathan M Irish
The monocyte phagocyte system (MPS) includes numerous monocyte, macrophage, and dendritic cell (DC) populations that are heterogeneous, both phenotypically and functionally. In this study, we sought to characterize those diverse MPS phenotypes with mass cytometry (CyTOF). To identify a deep phenotype of monocytes, macrophages, and DCs, a panel was designed to measure 38 identity, activation, and polarization markers, including CD14, CD16, HLA-DR, CD163, CD206, CD33, CD36, CD32, CD64, CD13, CD11b, CD11c, CD86, and CD274...
April 11, 2017: Journal of Leukocyte Biology
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