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Myeloid-derived suppressor cells

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https://www.readbyqxmd.com/read/28634284/co-administration-of-rankl-and-ctla4-antibodies-enhances-lymphocyte-mediated-anti-tumor-immunity-in-mice
#1
Elizabeth Ahern, Heidi Harjunpaa, Deborah Barkauskas, Stacey Allen, Kazuyoshi Takeda, Hideo Yagita, David Wyld, William C Dougall, Michele W L Teng, Mark J Smyth
Purpose: Novel partners for established immune checkpoint inhibitors in the treatment of cancer are needed to address the problems of primary and acquired resistance. The efficacy of combination RANKL and CTLA4 blockade in anti-tumor immunity has been suggested by recent case reports in melanoma. Here we provide a rationale for this combination in mouse models of cancer. <br />Experimental Design: The efficacy and mechanism of a combination of RANKL and CTLA4 blockade was examined by tumor infiltrating lymphocyte analysis, tumor growth and metastasis using a variety of neutralizing antibodies and gene-targeted mice...
June 20, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28624842/increased-levels-of-pro-inflammatory-and-anti-inflammatory-cellular-responses-in-parkinson-s-disease-patients-search-for-a-disease-indicator
#2
Likun Yang, Changfeng Guo, Jie Zhu, Yi Feng, Weiliang Chen, Zhizhong Feng, Dan Wang, Shibai Sun, Wei Lin, Yuhai Wang
BACKGROUND Parkinson's disease (PD) is the second most prevalent neurodegenerative disorder and it arises when most of the dopaminergic neurons of substantia nigra region die. Several mechanisms have been postulated as the causative event in PD pathology, and neuroinflammation is most crucial among them. MATERIAL AND METHODS We analyzed T-helper 17 (Th17) cells and myeloid-derived suppressor cells (MDSCs) from 80 PD patients to assess inflammatory processes and to find a cost-effective means to evaluate PD prognosis...
June 18, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/28619949/expansion-and-activation-of-granulocytic-myeloid-derived-suppressor-cells-in-childhood-precursor-b-cell-acute-lymphoblastic-leukemia
#3
Yu-Feng Liu, Ying-Ying Chen, Ying-Yi He, Jia-Yi Wang, Jian-Ping Yang, Shu-Ling Zhong, Nan Jiang, Pan Zhou, Hua Jiang, Jie Zhou
Precursor B cell acute lymphoblastic leukemia (B-ALL) is a B cell-derived, malignant disorder with the highest incidence among children. In addition to the genetic abnormality, a dysregulated immune system also has an important role in the pathogenesis of B-ALL. Myeloid-derived suppressor cells (MDSCs) represent one of the key drivers in immune tolerance against tumor cells, including various solid tumors and hematologic malignancies. The role of MDSCs in B-ALL remains poorly understood. Here, we showed that the granulocytic (G)-MDSC population was significantly elevated in both the peripheral blood and BM of patients with B-ALL, when compared with age-matched healthy controls...
June 15, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28618162/zeb1-regulated-inflammatory-phenotype-in-breast-cancer-cells
#4
Akihiro Katsura, Yusuke Tamura, Satoshi Hokari, Mayumi Harada, Masato Morikawa, Tsubasa Sakurai, Kei Takahashi, Anna Mizutani, Jun Nishida, Yuichiro Yokoyama, Yasuyuki Morishita, Takashi Murakami, Shogo Ehata, Kohei Miyazono, Daizo Koinuma
Zinc finger E-box binding protein 1 (ZEB1) and ZEB2 induce epithelial-mesenchymal transition (EMT) and enhance cancer progression. However, the global view of transcriptional regulation by ZEB1 and ZEB2 is yet to be elucidated. Here, we identified a ZEB1-regulated inflammatory phenotype in breast cancer cells using chromatin immunoprecipitation-sequencing and RNA sequencing, followed by gene set enrichment analysis (GSEA) of ZEB1-bound genes. Knockdown of ZEB1 and/or ZEB2 resulted in the down-regulation of genes encoding inflammatory cytokines related to poor prognosis in cancer patients, including IL6 and IL8, therefore suggesting that ZEB1 and ZEB2 have similar functions in terms of the regulation of production of inflammatory cytokines...
June 15, 2017: Molecular Oncology
https://www.readbyqxmd.com/read/28612394/tumor-associated-with-cd70-expression-is-involved-in-promoting-tumor-migration-and-macrophage-infiltration-in-gbm
#5
Haitao Ge, Luyan Mu, Linchun Jin, Changlin Yang, Yifan Emily Chang, Yu Long, Gabriel De Leon, Loic Deleyrolle, Duane A Mitchell, Paul S Kubilis, Dunyue Lu, Jiping Qi, Yunhe Gu, Zhiguo Lin, Jianping Huang
Tumor migration/metastasis and immunosuppression are major obstacles in effective cancer therapy. Incidentally, these 2 hurdles usually coexist inside tumors, therefore making therapy significantly more complicated, as both oncogenic mechanisms must be addressed for successful therapeutic intervention. Our recent report highlights that the tumor expression of a TNF family member, CD70, is correlated with poor survival for primary gliomas. In this study, we investigated how CD70 expression by GBM affects the characteristics of tumor cells and the tumor microenvironment...
June 13, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28611302/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...
May 30, 2017: Oncotarget
https://www.readbyqxmd.com/read/28605567/mir-30a-increases-mdsc-differentiation-and-immunosuppressive-function-by-targeting-socs3-in-mice-with-b-cell-lymphoma
#7
Zhen Xu, Jianjian Ji, Jingjing Xu, Dan Li, Guoping Shi, Fei Liu, Liang Ding, Jing Ren, Huan Dou, Tingting Wang, Yayi Hou
Myeloid-derived suppressor cells (MDSCs), including granulocytic (G)-MDSCs and monocytic (M)-MDSCs, play a critical role in tumor-induced T cell tolerance. MDSCs immunosuppressive function and differentiation are significantly promoted in patients and B-cell lymphoma model mice. However, the mechanisms regulating these processes remain largely unclear. In this study, we observed increased microRNA (miR)-30a expression both in G-MDSCs and in M-MDSCs from B cell lymphoma model mice. After transfection with miR-30a mimics, the differentiation and suppressive capacities of MDSCs were significantly increased via up-regulation of arginase-1...
June 12, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28599501/microrna-217-inhibits-cell-proliferation-and-enhances-chemosensitivity-to-doxorubicin-in-acute-myeloid-leukemia-by-targeting-kras
#8
Yi Xiao, Taoran Deng, Changliang Su, Zhen Shang
Acute myeloid leukemia (AML) is a heterogeneous malignant disorder derived from the myeloid hematopoietic cells that accounts for ~80% of all adult acute leukemia. Numerous studies have shown that drug resistance not only exists against conventional chemotherapeutic drugs, but also limits the efficacy of new biological agents. Therefore, it is important to identify the mechanisms behind chemoresistance and seek therapeutic strategies to enhance efficacy in AML chemotherapy. MicroRNA (miR)-217 has been recognized as a tumor suppressor that is downregulated in various types of cancer, however the mechanisms behind the expression and function of miR-217 in AML have not yet been recognized...
June 2017: Oncology Letters
https://www.readbyqxmd.com/read/28599274/trans-sialidase-based-vaccine-candidate-protects-against-trypanosoma-cruzi-infection-not-only-inducing-an-effector-immune-response-but-also-affecting-cells-with-regulatory-suppressor-phenotype
#9
Estefanía Prochetto, Carolina Roldán, Iván A Bontempi, Daiana Bertona, Luz Peverengo, Miguel H Vicco, Luz M Rodeles, Ana R Pérez, Iván S Marcipar, Gabriel Cabrera
Prophylactic and/or therapeutic vaccines have an important potential to control Trypanosoma cruzi (T. cruzi)infection. The involvement of regulatory/suppressor immune cells after an immunization treatment and T. cruzi infection has never been addressed. Here we show that a new trans-sialidase-based immunogen (TSf) was able to confer protection, correlating not only with beneficial changes in effector immune parameters, but also influencing populations of cells related to immune control.Regarding the effector response, mice immunized with TSf showed a TS-specific antibody response, significant delayed-type hypersensitivity (DTH) reactivity and increased production of IFN-γ by CD8+ splenocytes...
May 25, 2017: Oncotarget
https://www.readbyqxmd.com/read/28595538/immune-cells-act-as-promising-targets-for-the-treatment-of-bone-metastasis
#10
Guojing Luo, Yuedong He, Qian Zhao, Xijie Yu
BACKGROUND: Bone metastasis is a common complication of certain types of cancer, and unfortunately, it is still incurable to date. Immune system is a major defence against tumor cells and bone metastasis. However, the immunodeficient mouse models are widely used in most researches of bone metastasis, thereby excluding the regulatory roles of the immune system in bone metastasis. OBJECTIVE: To provide a comprehensive overview on the cellular and molecular mechanisms by which immune cells interact with tumor cells and bone cells, as well as recent related patents...
June 6, 2017: Recent Patents on Anti-cancer Drug Discovery
https://www.readbyqxmd.com/read/28592438/cd14-cd15-hla-dr-myeloid-derived-suppressor-cells-impair-antimicrobial-responses-in-patients-with-acute-on-chronic-liver-failure
#11
Christine Bernsmeier, Evangelos Triantafyllou, Robert Brenig, Fanny J Lebosse, Arjuna Singanayagam, Vishal C Patel, Oltin T Pop, Wafa Khamri, Rooshi Nathwani, Robert Tidswell, Christopher J Weston, David H Adams, Mark R Thursz, Julia A Wendon, Charalambos Gustav Antoniades
OBJECTIVE: Immune paresis in patients with acute-on-chronic liver failure (ACLF) accounts for infection susceptibility and increased mortality. Immunosuppressive mononuclear CD14(+)HLA-DR(-) myeloid-derived suppressor cells (M-MDSCs) have recently been identified to quell antimicrobial responses in immune-mediated diseases. We sought to delineate the function and derivation of M-MDSC in patients with ACLF, and explore potential targets to augment antimicrobial responses. DESIGN: Patients with ACLF (n=41) were compared with healthy subjects (n=25) and patients with cirrhosis (n=22) or acute liver failure (n=30)...
June 7, 2017: Gut
https://www.readbyqxmd.com/read/28591224/low-dose-glucocorticoids-suppresses-ovarian-tumor-growth-and-metastasis-in-an-immunocompetent-syngeneic-mouse-model
#12
Kai-Ti Lin, Shu-Pin Sun, Jui-I Wu, Lu-Hai Wang
Ovarian cancer has the highest mortality rate among gynecologic malignancies. Despite chemotherapy and surgical debulking options, ovarian cancer recurs and disseminates frequently with a poor prognosis. We previously reported a novel role of glucocorticoids (GCs) in metastatic ovarian cancer by upregulating microRNA-708. In this study, we used an immunocompetent syngeneic mouse model and further evaluated the effect and optimal dosages of GCs in treating metastatic ovarian cancer. The treatment of C57BL/6-derived ovarian cancer ID-8 cells with a synthetic GC, dexamethasone (DEX), induced the expression of microRNA-708, leading to decreased cell migration and invasion through targeting Rap1B...
2017: PloS One
https://www.readbyqxmd.com/read/28582845/elevated-lactate-dehydrogenase-ldh-can-be-a-marker-of-immune-suppression-in-cancer-interplay-between-hematologic-and-solid-neoplastic-clones-and-their-microenvironments
#13
Jennifer Ding, Judith E Karp, Ashkan Emadi
Metabolism of neoplastic cells is shifted toward high glucose uptake and enhanced lactate production. Lactate dehydrogenase (LDH), which is comprised of two major subunits, LDH-A and LDH-B, reversibly catalyzes the conversion of pyruvate to lactate or lactate to pyruvate. LDH-A has a higher affinity for pyruvate and is a key enzyme in the glycolytic pathway. Elevated LDH is a negative prognostic biomarker not only because it is a key enzyme involved in cancer metabolism, but also because it allows neoplastic cells to suppress and evade the immune system by altering the tumor microenvironment...
May 19, 2017: Cancer Biomarkers: Section A of Disease Markers
https://www.readbyqxmd.com/read/28579805/bisdemethoxycurcumin-in-combination-with-%C3%AE-pd-l1-antibody-boosts-immune-response-against-bladder-cancer
#14
Yiqun Shao, Wenjing Zhu, Jun Da, Mingxi Xu, Yiwei Wang, Juan Zhou, Zhong Wang
Curcumin was recently discovered to strengthen immune response through multiple mechanisms. Cytotoxic CD8(+) T-cells play a critical role in modulating anticancer immune response, but is severely restricted by T-cell exhaustion. Bladder carcinomas express PD-L1 and can abrogate CD8(+) T-cell response. Thus, we hypothesized that bisdemethoxycurcumin, a natural dimethoxy derivative of curcumin, may provide a favorable environment for T-cell response against bladder cancer when used in combination with α-PD-L1 antibody...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28570288/myeloid-derived-suppressor-cells-associated-with-disease-progression-in-primary-hiv-infection-pd-l1-blockade-attenuates-inhibition
#15
Zi-Ning Zhang, Nan Yi, Tong-Wei Zhang, Le-Le Zhang, Xian Wu, Mei Liu, Ya-Jing Fu, Si-Jia He, Yong-Jun Jiang, Hai-Bo Ding, Zhen-Xing Chu, Hong Shang
OBJECTIVE: Events occurring during the initial phase of human immunodeficiency virus (HIV) infection are intriguing because of their dramatic impact on the subsequent course of the disease. In particular, the relationship between myeloid-derived suppressor cells (MDSCs) and HIV pathogenesis in primary infection remains unknown and the mechanism of MDSCs in HIV infection are incompletely defined. METHODS: The frequency of MDSC expression in patients with primary (PHI) and chronic HIV infection was measured, and the association with disease progression was studied...
May 31, 2017: Journal of Acquired Immune Deficiency Syndromes: JAIDS
https://www.readbyqxmd.com/read/28551851/the-ratio-of-hla-dr-and-vnn2-expression-on-cd14-myeloid-derived-suppressor-cells-can-distinguish-glioblastoma-from-radiation-necrosis-patients
#16
David C Soler, Andrew B Young, Kevin D Cooper, Amber Kerstetter-Fogle, Jill S Barnholtz-Sloan, Haley Gittleman, Thomas S McCormick, Andrew E Sloan
Glioblastoma (GBM) is the most aggressive and lethal type of brain cancer with a median survival of less than two years even following aggressive treatment (Stupp et al., N Engl J Med 352:987-996, 2005). Among the many challenges in treating patients with this devastating disease is the ability to differentiate Magnetic Resonance Imaging (MRI) images that appear following radiation therapy, often termed "radiation necrosis" from true GBM recurrence. Radiation necrosis (RN) and GBM are very difficult to distinguish and currently only a brain biopsy can conclusively differentiate these pathologies...
May 27, 2017: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/28546500/myeloid-derived-suppressor-cells-a-new-therapeutic-target-to-overcome-resistance-to-cancer-immunotherapy
#17
REVIEW
Jason A Chesney, Robert A Mitchell, Kavitha Yaddanapudi
Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of immature myeloid cells that accumulate during pathologic conditions, such as cancer. Patients diagnosed with advanced metastatic cancers have an average survival of 12-24 mo, a survival time that hasn't changed significantly in the past 30 yr. Despite some encouraging improvements in response rates and overall survival in patients receiving immunotherapies, such as immune checkpoint inhibitors, most patients will ultimately progress...
May 25, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28536706/plasma-levels-of-high-mobility-group-box-1-during-peptide-vaccination-in-patients-with-recurrent-ovarian-cancer
#18
Kayoko Waki, Kouichiro Kawano, Naotake Tsuda, Kimio Ushijima, Kyogo Itoh, Akira Yamada
High-mobility group box 1 (HMGB1) is a nuclear protein that is known to be secreted into extracellular fluids from injured cells, activated macrophages, and tumor cells. The clinical correlation of circulating HMGB1 levels with various diseases including cancer has been reported. However, there is no information on HMGB1 levels in cancer patients treated with peptide vaccination. In the present study, we investigated the plasma levels of HMGB1 during personalized peptide vaccination in patients with recurrent ovarian cancer...
2017: Journal of Immunology Research
https://www.readbyqxmd.com/read/28536308/immune-correlates-of-gm-csf-and-melanoma-peptide-vaccination-in-a-randomized-trial-for-the-adjuvant-therapy-of-resected-high-risk-melanoma-e4697
#19
Lisa H Butterfield, Fengmin Zhao, Sandra Lee, Ahmad A Tarhini, Kim A Margolin, Richard L White, Michael Atkins, Gary I Cohen, Theresa L Whiteside, John M Kirkwood, David H Lawson
Purpose: E4697 was a multi-center intergroup randomized placebo-controlled Phase III trial of adjuvant GM-CSF and/or a multi-epitope melanoma peptide vaccine for patients with completely resected, high-risk stage III/IV melanoma. <p>Experimental Design: 815 patients were enrolled from 12/99 to 10/06 into this 6-arm study. GM-CSF was chosen to promote the numbers and functions of dendritic cells (DC). The melanoma antigen peptide vaccine (Tyrosinase368-376 (370D), gp100209-217 (210M), MART-127-35) in Montanide was designed to promote melanoma specific CD8(+) T cell responses...
May 23, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28535011/tumor-growth-limited-to-subcutaneous-site-vs-tumor-growth-in-pulmonary-site-exhibit-differential-effects-on-systemic-immunities
#20
Junko Masuda, Eiji Takayama, Warren Strober, Ayano Satoh, Yuji Morimoto, Yasuko Honjo, Tatsuo Ichinohe, Shin-Ichi Tokuno, Toshiaki Ishizuka, Takahiro Nakata, Akifumi Mizutani, Naoki Umemura, Atsushi Kitani, Ivan J Fuss, Tsukasa Shigehiro, Harumi Kawaki, Masako Mizuno-Kamiya, Nobuo Kondoh, Masaharu Seno
To evaluate systemic immunity associated with tumor growth limited to a subcutaneous site versus growth proceeding at multiple tumor sites, we established syngeneic mouse subcutaneous and pulmonary tumor models by local subcutaneous and intravenous injection of colon carcinoma CT26 cells. We found that splenic myeloid-derived suppressor cell (MDSC) levels were significantly increased in the subcutaneous tumor model but not in the pulmonary tumor model. Furthermore, both CD4+ and CD8+ T cells as well as CD4+ Foxp3+ T cells were significantly decreased in the subcutaneous tumor model and were largely unchanged in the pulmonary tumor model...
May 17, 2017: Oncology Reports
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