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https://www.readbyqxmd.com/read/27926489/suppression-of-immune-regulatory-cells-with-combined-therapy-of-celecoxib-and-sunitinib-in-renal-cell-carcinoma
#1
Qi Zhao, Jianming Guo, Guomin Wang, Yiwei Chu, Xiaoyi Hu
OBJECTIVE: To observe the the potential benefit of sunitinib in combination with cyclooxygenase-2(COX-2) inhibitor in renal cell carcinoma therapy. METHODS: 769-p cell lines were treated with sunitinib, celecoxib, or in combination at different concentrations respectively. We investigated the expression of granulocyte-macrophage colony stimulating factor (GM-CSF) in 769-p and cell proliferation in vitro. BALB/c mice implanted with Renca cells were divided into 4 groups and administered orally by gavage with sunitinib, COX-2 inhibitor (celecoxib) monotherapy or combination, and PBS respectively...
December 2, 2016: Oncotarget
https://www.readbyqxmd.com/read/27922687/immature-myeloid-derived-suppressor-cells-a-bridge-between-inflammation-and-cancer-review
#2
Caterina Musolino, Alessandro Allegra, Govanni Pioggia, Sebastiano Gangemi
Chronic inflammation is considered to be one of the hallmarks of tumor initiation and progression. Changes occurring in the microenvironment of progressing tumors resemble the process of chronic inflammation, which begins with ischemia followed by interstitial and cellular edema, appearance of immune cells, growth of blood vessels and tissue repair, and development of inflammatory infiltrates. Moreover, long‑term production and accumulation of inflammatory factors lead to local and systemic immunosuppression associated with cancer progression...
December 5, 2016: Oncology Reports
https://www.readbyqxmd.com/read/27909978/il-17a-produced-by-peritoneal-macrophages-promote-the-accumulation-and-function-of-granulocytic-myeloid-derived-suppressor-cells-in-the-development-of-colitis-associated-cancer
#3
Yue Zhang, Juan Wang, Wenxin Wang, Jie Tian, Kai Yin, Xinyi Tang, Jie Ma, Huaxi Xu, Shengjun Wang
It is widely acknowledged that a close relationship is between inflammation and colon cancer. Interleukin (IL)-17A and myeloid-derived suppressor cells (MDSCs) play an important role in the development of colitis-associated cancer (CAC). However, the precise changes of IL-17, MDSCs, and Th17 cells during the CAC progression have not been observed in the colorectal chronic inflammation-dependent tumor. In this study, we found the level of IL-17 was increased in pathogenic colon site during the early stage of CAC model...
December 1, 2016: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/27904768/combined-vegfr-and-ctla-4-blockade-increases-the-antigen-presenting-function-of-intratumoral-dcs-and-reduces-the-suppressive-capacity-of-intratumoral-mdscs
#4
Stephanie Du Four, Sarah K Maenhout, Simone P Niclou, Kris Thielemans, Bart Neyns, Joeri L Aerts
Melanoma brain metastases (MBM) occur in 10% to 50% of melanoma patients. They are often associated with a high morbidity and despite the improvements in the treatment of advanced melanoma, including immunotherapy, patients with MBM still have a poor prognosis. Antiangiogenic treatment was shown to reduce the immunosuppressive tumor microenvironment. Therefore we investigated the effect of the combination of VEGFR- and CTLA-4 blockade on the immune cells within the tumor microenvironment. In this study we investigated the effect of the combination of axitinib, a TKI against VEGFR-1, -2 and -3, with therapeutic inhibition of CTLA-4 in subcutaneous and intracranial mouse melanoma models...
2016: American Journal of Cancer Research
https://www.readbyqxmd.com/read/27886105/pro-tumoral-inflammatory-myeloid-cells-as-emerging-therapeutic-targets
#5
REVIEW
Gabor J Szebeni, Csaba Vizler, Lajos I Nagy, Klara Kitajka, Laszlo G Puskas
Since the observation of Virchow, it has long been known that the tumor microenvironment constitutes the soil for the infiltration of inflammatory cells and for the release of inflammatory mediators. Under certain circumstances, inflammation remains unresolved and promotes cancer development. Here, we review some of these indisputable experimental and clinical evidences of cancer related smouldering inflammation. The most common myeloid infiltrate in solid tumors is composed of myeloid-derived suppressor cells (MDSCs) and tumor-associated macrophages (TAMs)...
November 23, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27885671/recruited-monocytic-myeloid-derived-suppressor-cells-promote-the-arrest-of-tumor-cells-in-the-premetastatic-niche-through-an-il-1%C3%AE-mediated-increase-in-e-selectin-expression
#6
Huifang Shi, Juechao Zhang, Xiaoqing Han, Huihan Li, Mingshu Xie, Yingying Sun, Wenguang Liu, Xueqing Ba, Xianlu Zeng
The tumor premetastatic niche initiated by primary tumors is constructed by multiple molecular factors and cellular components and provides permissive condition that allows circulating tumor cells to successfully metastasize. Myeloid-derived suppressor cells (MDSCs), a population of immature cells in pathological conditions, play a critical role in the formation of the premetastatic niche. However, few researches are focused on the function of monocytic MDSCs (mo-MDSCs), a subtype of MDSCs, in the construction of the niche...
November 25, 2016: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/27880732/ceramide-activates-lysosomal-cathepsin-b-and-cathepsin-d-to-attenuate-autophagy-and-induces-er-stress-to-suppress-myeloid-derived-suppressor-cells
#7
Feiyan Liu, Xia Li, Chunwan Lu, Aiping Bai, Jacek Bielawski, Alicja Bielawska, Brendan Marshall, Patricia V Schoenlein, Iryna O Lebedyeva, Kebin Liu
Myeloid-derived suppressor cells (MDSCs) are immune suppressive cells that are hallmarks of human cancer. MDSCs inhibit cytotoxic T lymphocytes (CTLs) and NK cell functions to promote tumor immune escape and progression, and therefore are considered key targets in cancer immunotherapy. Recent studies determined a key role of the apoptosis pathways in tumor-induced MDSC homeostasis and it is known that ceramide plays a key role in regulation of mammalian cell apoptosis. In this study, we aimed to determine the efficacy and underlying molecular mechanism of ceramide in suppression of MDSCs...
November 17, 2016: Oncotarget
https://www.readbyqxmd.com/read/27877014/prognostic-potential-of-an-immune-score-based-on-the-density-of-cd8-t-cells-cd20-b-cells-and-cd33-p-stat1-double-positive-cells-and-hmgb1-expression-within-cancer-nests-in-stage-iiia-gastric-cancer-patients
#8
Jun Dong, Jiao Li, Shiming Liu, Xingyu Feng, Shi Chen, Zhiwei Zhou, Yingbo Chen, Xiaoshi Zhang
OBJECTIVE: There is heterogeneity in the prognosis of gastric cancers staged according to the tumornodes- metastasis (TNM) system. This study evaluated the prognostic potential of an immune score system to supplement the TNM staging system. METHODS: An immunohistochemical analysis was conducted to assess the density of T cells, B cells, and myeloid-derived suppressor cells (MDSCs) in cancer tissues from 100 stage IIIA gastric cancer patients; the expression of the high-mobility group protein B1 (HMGB1) was also evaluated in cancer cells...
October 2016: Chinese Journal of Cancer Research, Chung-kuo Yen Cheng Yen Chiu
https://www.readbyqxmd.com/read/27875974/nanoparticle-systems-modulating-myeloid-derived-suppressor-cells-for-cancer-immunotherapy
#9
Avia Wilkerson, Julian Kim, Alex Y Huang, Mei Zhang
Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of immature myeloid cells that are preferentially expanded in cancer. They arise from myeloid progenitor cells that do not differentiate into mature dendritic cells (DCs), granulocytes, or macrophages, and are rather thought to play a pivotal role in immune escape and cancer progression. MDSCs are characterized by the ability to suppress T cell proliferation and cytotoxicity, inhibit natural killer T (NKT) cell activation, and induce the differentiation and expansion of regulatory T cells (Treg)...
November 22, 2016: Current Topics in Medicinal Chemistry
https://www.readbyqxmd.com/read/27868073/the-crosstalk-between-myeloid-derived-suppressor-cells-and-immune-cells-to-establish-immune-tolerance-in-transplantation
#10
REVIEW
Chao Zhang, Shuo Wang, Cheng Yang, Ruiming Rong
Myeloid derived suppressor cells (MDSCs) are a heterogeneous population of myeloid precursor and progenitor cells and endowed with a robust immunosuppressive activity in multiple pathophysiological conditions. Recent studies have uncovered the crosstalk between MDSCs and immune cells (i.e., natural killer cells, dendritic cells, macrophages, natural killer T cells, and regulatory T cells) and its role in the establishment and maintenance of immune tolerant microenvironment in transplantation. Considering their strong immunosuppressive capability, MDSCs could become a prospective clinical regimen during transplantation tolerance induction, resulting in long-term graft survival with decreased or without immunosuppressive drugs...
2016: Journal of Immunology Research
https://www.readbyqxmd.com/read/27863995/tumor-targeted-delivery-of-sunitinib-base-enhances-vaccine-therapy-for-advanced-melanoma-by-remodeling-the-tumor-microenvironment
#11
Meirong Huo, Yan Zhao, Andrew Benson Satterlee, Yuhua Wang, Ying Xu, Leaf Huang
Development of an effective treatment against advanced tumors remains a major challenge for cancer immunotherapy. We have previously developed a potent mannose-modified lipid calcium phosphate (LCP) nanoparticle (NP)-based Trp2 vaccine for melanoma therapy, but because this vaccine can induce a potent anti-tumor immune response only during the early stages of melanoma, poor tumor growth inhibition has been observed in more advanced melanoma models, likely due to the development of an immune-suppressive tumor microenvironment (TME)...
November 15, 2016: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/27861788/phenotypically-resembling-myeloid-derived-suppressor-cells-are-increased-in-children-with-hiv-and-exposed-infected-with-mycobacterium-tuberculosis
#12
Nelita Du Plessis, Ruschca Jacobs, Andrea Gutschmidt, Zhuo Fang, Paul D van Helden, Manfred B Lutz, Anneke C Hesseling, Gerhard Walzl
Increased disease susceptibility during early life has been linked to immune immaturity, regulatory T-cell/TH2 immune biasing and hyporesponsiveness. The contribution of myeloid derived suppressor cells (MDSCs) remains uninvestigated. Here, we assessed peripheral MDSC in HIV-infected and -uninfected children with tuberculosis (TB) disease before, during and after TB treatment, along with matched household contacts (HHCs), HIV-exposed, -infected and -uninfected children without recent TB exposure. Serum analytes and enzymes associated with MDSC accumulation/activation/function were measured by colorimetric- and fluorescence arrays...
November 8, 2016: European Journal of Immunology
https://www.readbyqxmd.com/read/27859042/hla-g-promotes-myeloid-derived-suppressor-cell-mdsc-accumulation-and-suppressive-activity-during-human-pregnancy-through-engagement-of-the-receptor-ilt4
#13
Natascha Köstlin, Anna-Lena Ostermeir, Bärbel Spring, Julian Schwarz, Alexander Marmé, Christina B Walter, Christian F Poets, Christian Gille
Establishing and maintaining maternal-fetal tolerance is essential for a successful pregnancy; failure of immunological adaptation to pregnancy leads to severe complications such as abortion or preterm delivery. Myeloid-derived suppressor cells (MDSCs) are innate immune cells that suppress T-cell responses, expand during pregnancy and thus may play a role in tolerance induction. Human leucocyte antigen G (HLA-G) is a major histocompatibility complex (MHC) I molecule with immune-modulatory properties, which is expressed during pregnancy...
November 10, 2016: European Journal of Immunology
https://www.readbyqxmd.com/read/27857157/inhibiting-mdsc-differentiation-from-bone-marrow-with-phytochemical-polyacetylenes-drastically-impairs-tumor-metastasis
#14
Wen-Chi Wei, Sheng-Yen Lin, Chun-Wen Lan, Yu-Chen Huang, Chih-Yu Lin, Pei-Wen Hsiao, Yet-Ran Chen, Wen-Chin Yang, Ning-Sun Yang
Myeloid-derived suppressor cells (MDSCs) are implicated in the promotion of tumor metastasis by protecting metastatic cancerous cells from immune surveillance and have thus been suggested as novel targets for cancer therapy. We demonstrate here that oral feeding with polyacetylenic glycosides (BP-E-F1) from the medicinal plant Bidens pilosa effectively suppresses tumor metastasis and inhibits tumor-induced accumulation of granulocytic (g) MDSCs, but does not result in body weight loss in a mouse mammary tumor-resection model...
November 18, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27857057/in-vitro-exploration-of-a-myeloid-derived-suppressor-cell-line-as-vehicle-for-cancer-gene-therapy
#15
S Denies, F Combes, C Ghekiere, S Mc Cafferty, L Cicchelero, N N Sanders
Recent research indicates that cell-mediated gene therapy can be an interesting method to obtain intratumoral expression of therapeutic proteins. This paper explores the possibility of using transfected myeloid-derived suppressor cells (MDSCs), derived from a murine cell line, as cellular vehicles for transporting plasmid DNA (pDNA) encoding interleukin-12 (IL-12) to tumors. Transfecting these cells via electroporation caused massive cell death. This was not due to electroporation-induced cell damage, but was mainly the result of the intracellular presence of plasmids...
November 18, 2016: Cancer Gene Therapy
https://www.readbyqxmd.com/read/27856250/ectopical-expression-of-fabp4-gene-can-induce-bovine-muscle-derived-stem-cells-adipogenesis
#16
Le Zhang, Yanfang Zhao, Yue Ning, Hongbao Wang, Linsen Zan
Fatty acid binding protein 4 (FABP4) plays a key role in Fatty acid catabolism in mammals. Findings from our previous studies have indicated that FABP4 neither affect the differentiation of bovine preadipocytes nor does it change the expression of upstream genes. To investigate whether ectopically expressed FABP4 can induces Muscle-Derived Stem Cells (MDSCs) lipid synthesis and understand the regulatory mechanism behind it. In this study, adenoviruses infection is achieved to ectopically expressed FABP4 in bovine MDSCs, RNA-seq analyses at the very early stages of induction were performed to reveal gene expression level changes during MDSCs transdifferentiation...
November 14, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27856191/avoiding-phagocytosis-related-artifact-in-myeloid-derived-suppressor-cell-t-lymphocyte-suppression-assays
#17
REVIEW
Ruth J Davis, Christopher Silvin, Clint T Allen
Myeloid-derived suppressor cells (MDSCs) have garnered much attention in recent years as a potential target for altering the immunosuppressive tumor microenvironment in a variety of solid tumor types. The ability to accurately assess the immunosuppressive capacity of MDSCs is fundamental to the development of therapeutic approaches aimed at disabling these immunosuppressive functions. In this article we provide evidence that the use of CD3/28 coated microbeads leads to artefactual T-lymphocyte suppression due to sequestration of beads by MDSCs isolated from the spleens of wild-type mice bearing subcutaneous syngeneic, carcinogen-induced oral cavity carcinomas...
November 14, 2016: Journal of Immunological Methods
https://www.readbyqxmd.com/read/27853654/tumor-necrosis-factor-links-chronic-obstructive-pulmonary-disease-and-k-ras-mutant-lung-cancer-through-induction-of-an-immunosuppressive-pro-tumor-microenvironment
#18
Lei Gong, Mauricio da Silva Caetano, Amber M Cumpian, Soudabeh Daliri, Alejandra Garza Flores, Seon Hee Chang, Cesar E Ochoa, Christopher M Evans, Zhentao Yu, Seyed Javad Moghaddam
Tumor necrosis factor (TNF) is known as an important regulator of tumor microenvironment and inflammation. TNF levels are markedly elevated in the bronchoalveolar lavage fluid (BALF) of patients with chronic obstructive pulmonary disease (COPD), which is an independent risk factor for lung cancer. We have previously shown that COPD-like airway inflammation promotes lung cancer in a K-ras mutant mouse model (CC-LR mouse). This was associated with a significant increase of neutrophils in BALF, accompanied by a marked increase in TNF level, suggesting a link between COPD, TNF, and lung cancer promotion...
2016: Oncoimmunology
https://www.readbyqxmd.com/read/27853649/cd24-blunts-oral-squamous-cancer-development-and-dampens-the-functional-expansion-of-myeloid-derived-suppressor-cells
#19
Caroline W Fugle, Yongliang Zhang, Feng Hong, Shaoli Sun, Caroline Westwater, Saleh Rachidi, Hong Yu, Elizabeth Garret-Mayer, Keith Kirkwood, Bei Liu, Zihai Li
CD24 expression has been implicated in the oncogenesis of multiple types of cancer and high tumor expression is considered a poor prognosis factor; however, the role of CD24 in oral cancer progression is unknown. Unlike other cancer types, we found that higher CD24 levels in human oral cancers are correlated to lower clinical stage and better overall survival. We then dissected the role of CD24 and mechanisms in oral cancer pathogenesis in mice using a genetic strategy and demonstrated that CD24 deficiency increased the oral cavity tumor burden in response to the carcinogen 4-nitroquioline 1-oxide (4-NQO)...
2016: Oncoimmunology
https://www.readbyqxmd.com/read/27846813/granulocyte-colony-stimulating-factor-treatment-ameliorates-lupus-nephritis-through-the-expansion-of-regulatory-t-cells
#20
Ji-Jing Yan, Enkthuya Jambaldorj, Jae-Ghi Lee, Joon Young Jang, Jung Min Shim, Miyeun Han, Tai Yeon Koo, Curie Ahn, Jaeseok Yang
BACKGROUND: Granulocyte colony-stimulating factor (G-CSF) can induce regulatory T cells (Tregs) as well as myeloid-derived suppressor cells (MDSCs). Despite the immune modulatory effects of G-CSF, results of G-CSF treatment in systemic lupus erythematosus are still controversial. We therefore investigated whether G-CSF can ameliorate lupus nephritis and studied the underlying mechanisms. METHODS: NZB/W F1 female mice were treated with G-CSF or phosphate-buffered saline for 5 consecutive days every week from 24 weeks of age, and were analyzed at 36 weeks of age...
November 15, 2016: BMC Nephrology
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