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https://www.readbyqxmd.com/read/29234059/p16ink4a-and-p21cip1-waf1-promote-tumour-growth-by-enhancing-myeloid-derived-suppressor-cells-chemotaxis
#1
Atsushi Okuma, Aki Hanyu, Sugiko Watanabe, Eiji Hara
p16Ink4a and p21Cip1/Waf1 act as tumour suppressors through induction of cellular senescence. However, senescence-independent roles of these CDK inhibitors are not well understood. Here, we report an unexpected function of p16Ink4 and p21Cip1/Waf1, namely, tumour promotion through chemotaxis. In monocytic myeloid-derived suppressor cells (Mo-MDSCs), p16Ink4 and p21Cip1/Waf1 are highly expressed and stimulate CX3CR1 chemokine receptor expression by preventing CDK-mediated phosphorylation and inactivation of SMAD3...
December 12, 2017: Nature Communications
https://www.readbyqxmd.com/read/29226090/inhibition-of-il-18-mediated-myeloid-derived-suppressor-cell-accumulation-enhances-anti-pd1-efficacy-against-osteosarcoma-cancer
#2
Ying Guan, Rui Zhang, Zhibin Peng, Daming Dong, Guojun Wei, Yansong Wang
Myeloid derived suppressor cells (MDSC) are very important in tumor immune evasion and they dramatically increased in peripheral blood of patients with osteosarcoma cancer. The association between MDSC and various cytokines has been studied in the peripheral blood. However, little is known about the mechanism drawing MDSC into tumor parenchyma. This study was to analyze the correlation between MDSC subsets and interleukin 18 (IL-18) level in osteosarcoma tumor model and its effect on the immunotherapy. MDSC were isolated from the blood and parenchyma and analyzed in the osteosarcoma tumor model...
November 2017: Journal of Bone Oncology
https://www.readbyqxmd.com/read/29218828/monocytic-myeloid-derived-suppressor-cells-as-prognostic-factor-in-chronic-myeloid-leukaemia-patients-treated-with-dasatinib
#3
Cesarina Giallongo, Nunziatina L Parrinello, Piera La Cava, Giuseppina Camiolo, Alessandra Romano, Marina Scalia, Fabio Stagno, Giuseppe A Palumbo, Roberto Avola, Giovanni Li Volti, Daniele Tibullo, Francesco Di Raimondo
Myeloid suppressor cells are a heterogeneous group of myeloid cells that are increased in patients with chronic myeloid leukaemia (CML) inducing T cell tolerance. In this study, we found that therapy with tyrosine kinase inhibitors (TKI) decreased the percentage of granulocytic MDSC, but only patients treated with dasatinib showed a significant reduction in the monocytic subset (M-MDSC). Moreover, a positive correlation was observed between number of persistent M-MDSC and the value of major molecular response in dasatinib-treated patients...
December 8, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/29215754/inhibition-of-jak2-stat3-reduces-tumor-induced-angiogenesis-and-myeloid-derived-suppressor-cells-in-head-and-neck-cancer
#4
Jian-Feng Liu, Wei-Wei Deng, Lei Chen, Yi-Cun Li, Lei Wu, Si-Rui Ma, Wen-Feng Zhang, Lin-Lin Bu, Zhi-Jun Sun
Angiogenesis is an essential event in tumor growth and metastasis, and immune system also contributes to the tumor evasion. Emerging evidences have suggested the bidirectional link between angiogenesis and immunosuppression. Myeloid-derived suppressor cell (MDSC) is a kind of immunosuppressive cells and plays an important role in this process. However, the actual regulatory mechanisms of angiogenesis and MDSCs in head and neck squamous cell carcinoma (HNSCC) were unclear. In this study, through analyzing the immunohistochemistry staining of human HNSCC tissue microarray, we found that the microvascular density (MVD) was significantly increased in HNSCC patients...
December 7, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/29211299/endoplasmic-reticulum-stress-induced-lox-1-cd15-polymorphonuclear-myeloid-derived-suppressor-cells-in-hepatocellular-carcinoma
#5
Nan Jiang, Yan-Fang Xing, Bo Hu, Jian-Xin Tang, Hui-Min Dong, Yu-Mei He, Dan-Yun Ruan, Qing-Jian Ye, Jia-Rong Cai, Xiao-Kun Ma, Jie Chen, Xiu-Rong Cai, Ze-Xiao Lin, Xiang-Yuan Wu, Xing Li
AIM: A recent study indicated that Lectin-type oxidized LDL receptor-1 (LOX-1) was a distinct surface marker for human polymorphonuclears myeloid-derived suppressor cells (PMN-MDSC). The present study was aimed to investigate the existence LOX-1 PMN-MDSC in hepatocellular carcinoma (HCC) patients. METHODS: 127 HCC patients, 10 patients with mild active chronic hepatits B, 10 liver cirrhosis due to hepatitis B, 10 liver dysplastic node with hepatitis B and 50 health control were included...
December 6, 2017: Immunology
https://www.readbyqxmd.com/read/29204699/therapeutic-reduction-of-cell-mediated-immunosuppression-in-mycosis-fungoides-and-s%C3%A3-zary-syndrome
#6
Larisa J Geskin, Oleg E Akilov, Soonyou Kwon, Michael Schowalter, Simon Watkins, Theresa L Whiteside, Lisa H Butterfield, Louis D Falo
Tumor progression is associated with progressive immunosuppression mediated in part by T regulatory cell(s) (Treg) and/or myeloid-derived suppressor cell(s) (MDSC). Development of strategies to reduce populations of immune cells with suppressive function in cancer patients may enable the induction or recovery of immunity against tumor cells, which may limit or reverse disease progression. With a goal of developing Treg and MDSC neutralizing strategies to treat mycosis fungoides (MF) and Sézary syndrome (SzS), we determined the association between disease stage and suppressor cell populations in patients with MF/SzS, including those responding to therapy...
December 4, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/29204146/intracellular-s100a9-promotes-myeloid-derived-suppressor-cells-during-late-sepsis
#7
Jun Dai, Ajinkya Kumbhare, Dima Youssef, Charles E McCall, Mohamed El Gazzar
Myeloid precursor cell reprogramming into a myeloid-derived suppressor cell (MDSC) contributes to high mortality rates in mouse and human sepsis. S100A9 mRNA and intracellular protein levels increase during early sepsis and remain elevated in Gr1+CD11b+ MDSCs after pro-inflammatory sepsis transitions to the later chronic anti-inflammatory and immunosuppressive phenotype. The purpose of this study was to determine whether intracellular S100A9 protein might sustain Gr1+CD11b+ MDSC repressor cell reprogramming during sepsis...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29196466/pmn-mdsc-infiltration-blocks-the-antitumor-effects-of-csf1r-inhibition
#8
(no author information available yet)
CSF1R inhibition both reduces protumorigenic TAMs and recruits protumorigenic PMN-MDSCs.
December 1, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/29184980/blockage-of-the-nlrp3-inflammasome-by-mcc950-improves-anti-tumor-immune-responses-in-head-and-neck-squamous-cell-carcinoma
#9
Lei Chen, Cong-Fa Huang, Yi-Cun Li, Wei-Wei Deng, Liang Mao, Lei Wu, Wen-Feng Zhang, Lu Zhang, Zhi-Jun Sun
The NLRP3 inflammasome is a critical innate immune pathway responsible for producing active interleukin (IL)-1β, which is associated with tumor development and immunity. However, the mechanisms regulating the inflammatory microenvironment, tumorigenesis and tumor immunity are unclear. Herein, we show that the NLRP3 inflammasome was over-expressed in human HNSCC tissues and that the IL-1β concentration was increased in the peripheral blood of HNSCC patients. Additionally, elevated NLRP3 inflammasome levels were detected in tumor tissues of Tgfbr1/Pten 2cKO HNSCC mice, and elevated IL-1β levels were detected in the peripheral blood serum, spleen, draining lymph nodes and tumor tissues...
November 28, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/29182438/high-numbers-of-myeloid-derived-suppressor-cells-in-peripheral-blood-and-ascitic-fluid-of-cirrhotic-and-hcc-patients
#10
Nadia Elwan, Mohamed Labib Salem, Abdelrahman Kobtan, Ferial El-Kalla, Loai Mansour, Mohamed Yousef, Ashraf Al-Sabbagh, Abdel-Aziz A Zidan, Sherief Abd-Elsalam
BACKGROUND: Hepatocellular carcinoma (HCC) is the 3rd most common cause of cancer-related death worldwide. It has evolved different immune escape mechanisms, which might include emergence of lymphoid and myeloid regulatory cells. Aim of this work: To determine the numbers of Myeloid-derived suppressor cells (MDSCs) in peripheral blood and ascitic fluid in cirrhosis and HCC and their relation to IFN-γ and α-fetoprotein (α-FP). PATIENTS AND METHODS: Sixty individuals were enrolled in this study; forty cirrhotic patients with ascites; twenty without HCC (Group I), and twenty with HCC (group II) as well as twenty healthy individuals as a control group (group III)...
November 28, 2017: Immunological Investigations
https://www.readbyqxmd.com/read/29172874/nfia-deletion-in-myeloid-cells-blocks-expansion-of-myeloid-derived-suppressor-cells-during-sepsis
#11
Jun Dai, Ajinkya Kumbhare, Danielle A Williams, Dima Youssef, Zhi Q Yao, Charles E McCall, Mohamed El Gazzar
Sepsis-induced immunosuppression increases the risk of chronic infection and reduces survival. Myeloid-derived suppressor cells (MDSCs) expand in the bone marrow and spleen during murine polymicrobial sepsis, contributing to immunosuppression. A better understanding of molecular controls of MDSC production is needed to identify treatment targets. We previously reported that miR-21 and miR-181b couple with transcription factor NFI-A to induce MDSCs during murine sepsis. Here, we expand upon these observations by showing that conditional deletion of the Nfia gene in the myeloid lineage precludes MDSC development...
January 1, 2017: Innate Immunity
https://www.readbyqxmd.com/read/29170400/host-sting-dependent-mdsc-mobilization-drives-extrinsic-radiation-resistance
#12
Hua Liang, Liufu Deng, Yuzhu Hou, Xiangjiao Meng, Xiaona Huang, Enyu Rao, Wenxin Zheng, Helena Mauceri, Matthias Mack, Meng Xu, Yang-Xin Fu, Ralph R Weichselbaum
Radiotherapy induces and promotes innate and adaptive immunity in which host STING plays an important role. However, radioresistance in irradiated tumors can also develop, resulting in relapse. Here we report a mechanism by which extrinsic resistance develops after local ablative radiation that relies on the immunosuppressive action of STING. The STING/type I interferon pathway enhances suppressive inflammation in tumors by recruiting myeloid cells in part via the CCR2 pathway. Germ-line knockouts of CCR2 or treatment with an anti-CCR2 antibody results in blockade of radiation-induced MDSC infiltration...
November 23, 2017: Nature Communications
https://www.readbyqxmd.com/read/29166041/molecular-origin-of-aging-of-pure-se-glass-growth-of-inter-chain-structural-correlations-network-compaction-and-partial-ordering
#13
S Dash, P Chen, P Boolchand
Glass transition width W of pure Se narrows from 7.1(3) °C to 1.5(2) °C and the non-reversing enthalpy of relaxation (ΔHnr) at Tg increases from 0.23(5) cal/g to 0.90(5) cal/g upon room temperature aging for 4 months in the dark as examined in modulated differential scanning colorimetry (MDSC) at low scan rates. In Raman scattering, such aging leads the A1 mode of Sen-chains (near 250 cm(-1)) to narrow by 26% and its scattering strength to decrease as the strength of modes of correlated chains (near 235 cm(-1)) and of Se8 rings (near 264 cm(-1)) systematically grows...
June 14, 2017: Journal of Chemical Physics
https://www.readbyqxmd.com/read/29147627/stat1-gene-deficient-mice-develop-accelerated-breast-cancer-growth-and-metastasis-which-is-reduced-by-il-17-blockade
#14
Sanjay Varikuti, Steve Oghumu, Mohamad Elbaz, Greta Volpedo, Dinesh K Ahirwar, Pablo C Alarcon, Rachel H Sperling, Ellen Moretti, Marissa S Pioso, Jennifer Kimble, Mohd W Nasser, Ramesh K Ganju, Cesar Terrazas, Abhay R Satoskar
Signal transducer and activator of transcription 1 (STAT1) mediates interferon gamma signaling which activates the expression of various genes related to apoptosis, inflammation, cell cycle and angiogenesis. Several experimental and clinical studies have investigated the role of STAT1 in primary tumor growth in breast cancer; however, its role in tumor metastasis remains to be determined. To determine the role of STAT1 in breast cancer metastasis, we analyzed growth and metastasis in WT or STAT1(-/-) mice orthotopically implanted with metastatic 4T1...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/29139571/human-prosthetic-joint-infections-are-associated-with-myeloid-derived-suppressor-cells-mdscs-implications-for-infection-persistence
#15
Cortney E Heim, Debbie Vidlak, Jessica Odvody, Curtis W Hartman, Kevin L Garvin, Tammy Kielian
Prosthetic joint infection (PJI) is a devastating complication of joint arthroplasty surgery typified by biofilm formation. Currently, mechanisms whereby biofilms persist and evade immune-mediated clearance in immune competent patients remain largely ill-defined. Therefore, the current study characterized leukocyte infiltrates and inflammatory mediator expression in tissues from patients with PJI compared to aseptic loosening. CD33(+) HLA-DR(-) CD66b(+) CD14(-/low) granulocytic myeloid-derived suppressor cells (G-MDSCs) were the predominant leukocyte population at sites of human PJI compared to aseptic tissues...
November 15, 2017: Journal of Orthopaedic Research: Official Publication of the Orthopaedic Research Society
https://www.readbyqxmd.com/read/29139296/differential-content-of-proteins-mrnas-and-mirnas-suggests-that-mdsc-and-their-exosomes-may-mediate-distinct-immune-suppressive-functions
#16
Lucia Geis-Asteggiante, Ashton T Belew, Virginia K Clements, Nathan J Edwards, Suzanne Ostrand-Rosenberg, Nagib M El-Sayed, Catherine Fenselau
Myeloid-derived suppressor cells (MDSC) are immature myeloid cells that accumulate in the circulation and the tumor microenvironment of most cancer patients. There, MDSC suppress both adaptive and innate immunity, hindering immunotherapies. The inflammatory milieu often present in cancers facilitates MDSC suppressive activity, causing aggressive tumor progression and metastasis. MDSC from tumor-bearing mice release exosomes, which carry biologically active proteins and mediate some of the immunosuppressive functions characteristic of MDSC...
November 15, 2017: Journal of Proteome Research
https://www.readbyqxmd.com/read/29137229/activation-of-vip-signaling-enhances-immunosuppressive-effect-of-mdscs-on-cmv-induced-adaptive-immunity
#17
Parvin Forghani, Christopher T Petersen, Edmund K Waller
Vasoactive intestinal peptide (VIP) is recognized as a potent anti-inflammatory factor which affects both the innate and adaptive arms of the immune system. These effects include, but are not limited to, inhibition of T cell proliferation and disruption of immune homeostasis. Myeloid-derived suppressor cells (MDSC) are an immune regulatory cell type that has been described in settings of cancer and infectious disease._Here we demonstrate a reduced circulating monocytic MDSCs in the VIP (-/-)vs. wild type MCMV...
October 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29136508/cancer-associated-fibroblasts-neutralize-the-anti-tumor-effect-of-csf1-receptor-blockade-by-inducing-pmn-mdsc-infiltration-of-tumors
#18
Vinit Kumar, Laxminarasimha Donthireddy, Douglas Marvel, Thomas Condamine, Fang Wang, Sergio Lavilla-Alonso, Ayumi Hashimoto, Prashanthi Vonteddu, Reeti Behera, Marlee A Goins, Charles Mulligan, Brian Nam, Neil Hockstein, Fred Denstman, Shanti Shakamuri, David W Speicher, Ashani T Weeraratna, Timothy Chao, Robert H Vonderheide, Lucia R Languino, Peter Ordentlich, Qin Liu, Xiaowei Xu, Albert Lo, Ellen Puré, Chunsheng Zhang, Andrey Loboda, Manuel A Sepulveda, Linda A Snyder, Dmitry I Gabrilovich
Tumor-associated macrophages (TAM) contribute to all aspects of tumor progression. Use of CSF1R inhibitors to target TAM is therapeutically appealing, but has had very limited anti-tumor effects. Here, we have identified the mechanism that limited the effect of CSF1R targeted therapy. We demonstrated that carcinoma-associated fibroblasts (CAF) are major sources of chemokines that recruit granulocytes to tumors. CSF1 produced by tumor cells caused HDAC2-mediated downregulation of granulocyte-specific chemokine expression in CAF, which limited migration of these cells to tumors...
November 13, 2017: Cancer Cell
https://www.readbyqxmd.com/read/29133913/nitric-oxide-mediated-inhibition-of-antigen-presentation-from-dcs-to-cd4-t-cells-in-cancer-and-measurement-of-stat1-nitration
#19
Joseph Markowitz, Jiang Wang, Zach Vangundy, Jia You, Vedat Yildiz, Lianbo Yu, Isaac P Foote, Owen E Branson, Andrew R Stiff, Taylor R Brooks, Brandon Biesiadecki, Thomas Olencki, Susheela Tridandapani, Michael A Freitas, Tracey Papenfuss, Mitch A Phelps, William E Carson
Myeloid derived suppressor cells (MDSC) produce nitric oxide (NO) and inhibit dendritic cell (DC) immune responses in cancer. DCs present cancer cell antigens to CD4(+) T cells through Jak-STAT signal transduction. In this study, NO donors (SNAP and DETA-NONOate) inhibited DC antigen presentation. As expected, MDSC isolated from peripheral blood mononuclear cells (PBMC) from cancer patients produced high NO levels. We hypothesized that NO producing MDSC in tumor-bearing hosts would inhibit DC antigen presentation...
November 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29133357/myeloid-derived-suppressor-cells-ameliorate-cyclosporine-a-induced-hypertension-in-mice
#20
Valorie L Chiasson, Kelsey R Bounds, Piyali Chatterjee, Lochana Manandhar, Abhinandan R Pakanati, Marcos Hernandez, Bilal Aziz, Brett M Mitchell
The calcineurin inhibitor cyclosporine A (CsA) suppresses the immune system but promotes hypertension, vascular dysfunction, and renal damage. CsA decreases regulatory T cells and this contributes to the development of hypertension. However, CsA's effects on another important regulatory immune cell subset, myeloid-derived suppressor cells (MDSCs), is unknown. We hypothesized that augmenting MDSCs would ameliorate the CsA-induced hypertension and vascular and renal injury and dysfunction and that CsA reduces MDSCs in mice...
November 13, 2017: Hypertension
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