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tumor induced immune suppression

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https://www.readbyqxmd.com/read/28818640/the-influence-of-physical-activity-in-the-anti-tumor-immune-response-in-experimental-breast-tumor
#1
Thiago M Bianco, Douglas R Abdalla, Chamberttan S Desidério, Sofie Thys, Cindy Simoens, John-Paul Bogers, Eddie F C Murta, Márcia A Michelin
This study aimed to investigate the influence of physical activity in innate immunity to conduce to an effective antitumoral immune response analyzing the phenotype and activation status of infiltrating cells. We analyzed the intracellular cytokines and the transcription factors of tumor infiltrating lymphocytes (TILS) and spleen leukocytes. The Nos2 gene expression was evaluated in spleen cells and futhermore the ROS production was measured and spleen cells; another cell evaluated was dendritic cells (TIDCs), their cytokines expression and membrane molecules; finally to understood the results obtained, we analysed the dendritic cells obtained from bone marrow...
August 14, 2017: Immunology Letters
https://www.readbyqxmd.com/read/28817117/increased-tumor-infiltrating-cd45ra-ccr7-regulatory-t-cell-subset-with-immunosuppressive-properties-foster-gastric-cancer-progress
#2
Fang-Yuan Mao, Hui Kong, Yong-Liang Zhao, Liu-Sheng Peng, Weisan Chen, Jin-Yu Zhang, Ping Cheng, Ting-Ting Wang, Yi-Pin Lv, Yong-Sheng Teng, Xiao-Long Fu, Yu-Gang Liu, Xiao-Long Wu, Chuan-Jie Hao, Nan You, Ping Luo, Pei-Wu Yu, Quan-Ming Zou, Gang Guo, Yuan Zhuang
Regulatory T cells (Tregs) are major components of tumor-infiltrating immune cells with potent immunosuppressive properties in gastric cancer (GC) microenvironment. However, different subsets of the Tregs and their relevance to GC are unknown. Here, we found that patients with GC showed a significantly higher Tregs infiltration in tumors, and CD45RA(-)CCR7(-) Treg subset constituted most tumor-infiltrating Tregs. Tumor-infiltrating CD45RA(-)CCR7(-) Treg subset with an effector/memory phenotype accumulated in tumors and expressed low level of HLA-DR...
August 17, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28815045/tumor-derived-exosomes-induce-cd8-t-cell-suppressors
#3
Brian T Maybruck, Lukas W Pfannenstiel, Marcela Diaz-Montero, Brian R Gastman
BACKGROUND: The suppressive nature of immune cells in the tumor microenvironment plays a major role in regulating anti-tumor immune responses. Our previous work demonstrated that a soluble factor from tumor cells is able to induce a suppressor phenotype (SP) in human CD8(+) T cells typified by loss of CD27/CD28 expression and acquisition of a potent suppressor function. The present study hypothesized that the soluble mechanism that is inducing the SP in CD8(+) T cells are tumor-derived exosomes (TDEs)...
2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28815044/agonist-anti-gitr-antibody-significantly-enhances-the-therapeutic-efficacy-of-listeria-monocytogenes-based-immunotherapy
#4
Rajeev Shrimali, Shamim Ahmad, Zuzana Berrong, Grigori Okoev, Adelaida Matevosyan, Ghazaleh Shoja E Razavi, Robert Petit, Seema Gupta, Mikayel Mkrtichyan, Samir N Khleif
BACKGROUND: We previously demonstrated that in addition to generating an antigen-specific immune response, Listeria monocytogenes (Lm)-based immunotherapy significantly reduces the ratio of regulatory T cells (Tregs)/CD4(+) and myeloid-derived suppressor cells (MDSCs) in the tumor microenvironment. Since Lm-based immunotherapy is able to inhibit the immune suppressive environment, we hypothesized that combining this treatment with agonist antibody to a co-stimulatory receptor that would further boost the effector arm of immunity will result in significant improvement of anti-tumor efficacy of treatment...
2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28813180/inflammatory-signaling-cascades-and-autophagy-in-cancer
#5
Teresa Monkkonen, Jayanta Debnath
Tumor-associated inflammation is predictive of poor prognosis and drives a variety of tumorigenic phenotypes, including tumor proliferation and survival, angiogenesis, invasiveness, and metastasis. Here, we review mammalian data addressing the interaction of macroautophagy/autophagy with key signaling cascades associated with tumor inflammation. Although our understanding of this area remains incomplete, certain inflammatory pathways have emerged as important mediators of the crosstalk between autophagy and inflammation in tumors...
August 16, 2017: Autophagy
https://www.readbyqxmd.com/read/28811825/ethanol-extract-of-mylabris-phalerata-inhibits-m2-polarization-induced-by-recombinant-il-4-and-il-13-in-murine-macrophages
#6
Hwan-Suck Chung, Bong-Seon Lee, Jin Yeul Ma
Mylabris phalerata (MP) is an insect used in oriental herbal treatments for tumor, tinea infections, and stroke. Recent studies have shown that tumor-associated macrophages (TAM) have detrimental roles such as tumor progression, angiogenesis, and metastasis. Although TAM has phenotypes and characteristics in common with M2-polarized macrophages, M1 macrophages have tumor suppression and immune stimulation effects. Medicines polarizing macrophages to M1 have been suggested to have anticancer effects via the modulation of the tumor microenvironment...
2017: Evidence-based Complementary and Alternative Medicine: ECAM
https://www.readbyqxmd.com/read/28808483/therapeutic-immune-monitoring-of-cd4-cd25-t-cells-in-chronic-myeloid-leukemia-patients-treated-with-tyrosine-kinase-inhibitors
#7
Ziyuan Lu, Na Xu, Xuan Zhou, Guanlun Gao, Lin Li, Jixian Huang, Yuling Li, Qisi Lu, Bolin He, Chengyun Pan, Xiaoli Liu
Tyrosine kinase inhibitors (TKIs), including imatinib, dasatinib and nilotinib, are effective forms of therapy for various types of solid cancers and Philadelphia chromosome-positive (Ph(+)) chronic myeloid leukemia. A number of TKIs have been known to have strong effects on T cells, particularly cluster of differentiation (CD) 4(+)CD25(+) T cells, also known as regulatory T cells (Tregs). There is currently a deficit in the available clinical data regarding this area of study. In the present study, a total of 108 peripheral blood samples were collected from patients with chronic myeloid leukemia (CML) at diagnosis (n=31), and at 3 and 6 months following treatment with TKI [imatinib (n=12), dasatinib (n=11) and nilotinib groups (n=8)] and healthy controls (n=15)...
August 2017: Oncology Letters
https://www.readbyqxmd.com/read/28807056/agonist-anti-gitr-antibody-significantly-enhances-the-therapeutic-efficacy-of-listeria-monocytogenes-based-immunotherapy
#8
Rajeev Shrimali, Shamim Ahmad, Zuzana Berrong, Grigori Okoev, Adelaida Matevosyan, Ghazaleh Shoja E Razavi, Robert Petit, Seema Gupta, Mikayel Mkrtichyan, Samir N Khleif
BACKGROUND: We previously demonstrated that in addition to generating an antigen-specific immune response, Listeria monocytogenes (Lm)-based immunotherapy significantly reduces the ratio of regulatory T cells (Tregs)/CD4(+) and myeloid-derived suppressor cells (MDSCs) in the tumor microenvironment. Since Lm-based immunotherapy is able to inhibit the immune suppressive environment, we hypothesized that combining this treatment with agonist antibody to a co-stimulatory receptor that would further boost the effector arm of immunity will result in significant improvement of anti-tumor efficacy of treatment...
August 15, 2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28806909/tumor-derived-exosomes-induce-cd8-t-cell-suppressors
#9
Brian T Maybruck, Lukas W Pfannenstiel, Marcela Diaz-Montero, Brian R Gastman
BACKGROUND: The suppressive nature of immune cells in the tumor microenvironment plays a major role in regulating anti-tumor immune responses. Our previous work demonstrated that a soluble factor from tumor cells is able to induce a suppressor phenotype (SP) in human CD8(+) T cells typified by loss of CD27/CD28 expression and acquisition of a potent suppressor function. The present study hypothesized that the soluble mechanism that is inducing the SP in CD8(+) T cells are tumor-derived exosomes (TDEs)...
August 15, 2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28803390/cancer-clonal-theory-immune-escape-and-their-evolving-roles-in-cancer-multi-agent-therapeutics
#10
REVIEW
Jonathan L Messerschmidt, Prianka Bhattacharya, Gerald L Messerschmidt
PURPOSE OF REVIEW: The knowledge base of malignant cell growth and resulting targets is rapidly increasing every day. Clonal theory is essential to understand the changes required for a cell to become malignant. These changes are then clues to therapeutic intervention strategies. Immune system optimization is a critical piece to find, recognize, and eliminate all cancer cells from the host. Only by administering (1) multiple therapies that counteract the cancer cell's mutational and externally induced survival traits and (2) by augmenting the immune system to combat immune suppression processes and by enhancing specific tumor trait recognition can cancer begin to be treated with a truly targeted focus...
August 12, 2017: Current Oncology Reports
https://www.readbyqxmd.com/read/28798777/mesenchymal-stem-cells-promote-metastasis-of-lung-cancer-cells-by-downregulating-systemic-antitumor-immune-response
#11
Marina Gazdic, Bojana Simovic Markovic, Nemanja Jovicic, Maja Misirkic-Marjanovic, Valentin Djonov, Vladimir Jakovljevic, Nebojsa Arsenijevic, Miodrag L Lukic, Vladislav Volarevic
Since majority of systemically administered mesenchymal stem cells (MSCs) become entrapped within the lungs, we used metastatic model of lung cancer, induced by intravenous injection of Lewis lung cancer 1 (LLC1) cells, to investigate the molecular mechanisms involved in MSC-mediated modulation of metastasis. MSCs significantly augmented lung cancer metastasis, attenuate concentrations of proinflammatory cytokines (TNF-α, IL-17), and increase levels of immunosuppressive IL-10, nitric oxide, and kynurenine in sera of LLC1-treated mice...
2017: Stem Cells International
https://www.readbyqxmd.com/read/28797638/a-novel-tnfaip8-gene-mediates-l-arginine-metabolism-in-apostichopus-japonicus
#12
Yina Shao, Huahui Chen, Miao Lv, Chenghua Li, Weiwei Zhang, Ye Li, Xuelin Zhao, Yongbo Bao
Tumor necrosis factor (TNF)-α-induced protein 8 (TNFAIP8) family is a newly identified protein with vital roles in maintaining immune homeostasis. In the current study, we first cloned and characterized a TNFAIP8 gene from the invertebrate sea cucumber Apostichopus japonicus. The gene was designated as AjTNFAIP8. The full-length cDNA of AjTNFAIP8 was 1455 bp long and encoded a matured protein of 201 amino acid residues. Structural analysis indicated that AjTNFAIP8 had a death effector domain (DED)-like domain and composed of six α-helices...
August 7, 2017: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/28795532/a-combination-of-anti-pd-l1-mab-plus-lm-llo-e6-vaccine-efficiently-suppresses-tumor-growth-and-metastasis-in-hpv-infected-cancers
#13
Po-Lin Lin, Ya-Min Cheng, De-Wei Wu, Yu-Ju Huang, Hun-Chi Lin, Chih-Yi Chen, Huei Lee
PD-1/PD-L1 immunotherapy is viewed as having clinical benefits in advanced cancers but is effective in only a few patients, suggesting that an efficient combination approach is needed to improve efficacy. Immunohistochemistry analysis indicated that PD-L1 expression was correlated with the E6 expression in tumors from 122 lung cancer patients. The poorest survival occurred in PD-L1-positive/E6-positive tumor. PD-L1 expression was increased by the expression of E6, but not the E7, oncoprotein in lung and cervical cancer cells...
August 9, 2017: Cancer Medicine
https://www.readbyqxmd.com/read/28794630/probiotics-protect-mice-from-cocrmo-particles-induced-osteolysis
#14
Zhenheng Wang, Kaiwen Xue, Maosheng Bai, Zhantao Deng, Jingjing Gan, Gang Zhou, Hongbo Qian, Nirong Bao, Jianning Zhao
Wear particle-induced inflammatory osteolysis is the primary cause of aseptic loosening, which is the most common reason for total hip arthroplasty (THA) failure in the med- and long term. Recent studies have suggested an important role of gut microbiota (GM) in modulating the host metabolism and immune system, leading to alterations in bone mass. Probiotic bacteria administered in adequate amounts can alter the composition of GM and confer health benefits to the host. Given the inflammatory osteolysis that occurs in wear debris-induced prosthesis loosening, we examined whether the probiotic Lactobacillus casei could reduce osteolysis in a mouse calvarial resorption model...
2017: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/28791021/reconstitution-of-t-cell-proliferation-under-arginine-limitation-activated-human-t-cells-take-up-citrulline-via-l-type-amino-acid-transporter-1-and-use-it-to-regenerate-arginine-after-induction-of-argininosuccinate-synthase-expression
#15
Anke Werner, Miriam Koschke, Nadine Leuchtner, Claudia Luckner-Minden, Alice Habermeier, Johanna Rupp, Christin Heinrich, Roland Conradi, Ellen I Closs, Markus Munder
In the tumor microenvironment, arginine is metabolized by arginase-expressing myeloid cells. This arginine depletion profoundly inhibits T cell functions and is crucially involved in tumor-induced immunosuppression. Reconstitution of adaptive immune functions in the context of arginase-mediated tumor immune escape is a promising therapeutic strategy to boost the immunological antitumor response. Arginine can be recycled in certain mammalian tissues from citrulline via argininosuccinate (ASA) in a two-step enzymatic process involving the enzymes argininosuccinate synthase (ASS) and argininosuccinate lyase (ASL)...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28790848/the-status-of-immunosuppression-in-patients-with-stage-iiib-or-iv-non-small-cell-lung-cancer-correlates-with-the-clinical-characteristics-and-response-to-chemotherapy
#16
Yuan Wang, Guo-Fang Hu, Zhe-Hai Wang
BACKGROUND: Indoleamine 2,3-dioxygenase (IDO) catalyzes the rate-limiting step of tryptophan (Trp) degradation via the kynurenine (Kyn) pathway, which inhibits the proliferation of T cells and induces the apoptosis of T cells, leading to immune tolerance. Therefore, IDO has been considered as the most important mechanism for tumor cells to escape from immune response. Previous studies suggested that IDO might be involved in the progression of tumor and resistance to chemotherapy. Several preclinical and clinical studies have proven that IDO inhibitors can regulate IDO-mediated tumor immune escape and potentiate the effect of chemotherapy...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28790345/oleate-but-not-stearate-induces-the-regulatory-phenotype-of-myeloid-suppressor-cells
#17
Hao Wu, Carl Weidinger, Franziska Schmidt, Jacqueline Keye, Marie Friedrich, Cansu Yerinde, Gerald Willimsky, Zhihai Qin, Britta Siegmund, Rainer Glauben
Tumor infiltrating myeloid cells play contradictory roles in the tumor development. Dendritic cells and classical activated macrophages support anti-tumor immune activity via antigen presentation and induction of pro-inflammatory immune responses. Myeloid suppressor cells (MSCs), for instance myeloid derived suppressor cells (MDSCs) or tumor associated macrophages play a critical role in tumor growth. Here, treatment with sodium oleate, an unsaturated fatty acid, induced a regulatory phenotype in the myeloid suppressor cell line MSC-2 and resulted in an increased suppression of activated T cells, paralleled by increased intracellular lipid droplets formation...
August 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28783698/maintenance-of-macrophage-transcriptional-programs-and-intestinal-homeostasis-by-epigenetic-reader-sp140
#18
Stuti Mehta, D Alexander Cronkite, Megha Basavappa, Tahnee L Saunders, Fatemeh Adiliaghdam, Hajera Amatullah, Sara A Morrison, Jose D Pagan, Robert M Anthony, Pierre Tonnerre, Georg M Lauer, James C Lee, Sreehaas Digumarthi, Lorena Pantano, Shannan J Ho Sui, Fei Ji, Ruslan Sadreyev, Chan Zhou, Alan C Mullen, Vinod Kumar, Yang Li, Cisca Wijmenga, Ramnik J Xavier, Terry K Means, Kate L Jeffrey
Epigenetic "readers" that recognize defined posttranslational modifications on histones have become desirable therapeutic targets for cancer and inflammation. SP140 is one such bromodomain- and plant homeodomain (PHD)-containing reader with immune-restricted expression, and single-nucleotide polymorphisms (SNPs) within SP140 associate with Crohn's disease (CD). However, the function of SP140 and the consequences of disease-associated SP140 SNPs have remained unclear. We show that SP140 is critical for transcriptional programs that uphold the macrophage state...
March 3, 2017: Science Immunology
https://www.readbyqxmd.com/read/28783661/citrullination-of-nf-%C3%AE%C2%BAb-p65-promotes-its-nuclear-localization-and-tlr-induced-expression-of-il-1%C3%AE-and-tnf%C3%AE
#19
Bo Sun, Nishant Dwivedi, Tyler J Bechtel, Janet L Paulsen, Aaron Muth, Mandar Bawadekar, Gang Li, Paul R Thompson, Miriam A Shelef, Celia A Schiffer, Eranthie Weerapana, I-Cheng Ho
Many citrullinated proteins are known autoantigens in rheumatoid arthritis, a disease mediated by inflammatory cytokines, such as tumor necrosis factor-α (TNFα). Citrullinated proteins are generated by converting peptidylarginine to peptidylcitrulline, a process catalyzed by the peptidylarginine deiminases (PADs), including PAD1 to PAD4 and PAD6. Several major risk factors for rheumatoid arthritis are associated with heightened citrullination. However, the physiological role of citrullination in immune cells is poorly understood...
June 9, 2017: Science Immunology
https://www.readbyqxmd.com/read/28782555/nrf2-suppresses-the-function-of-dendritic-cells-to-facilitate-the-immune-escape-of-glioma-cells
#20
Jialiang Wang, Peng Liu, Shaoyan Xin, Zongbao Wang, Jun Li
Nrf2 is presented in dendritic cells (DCs) and contributes to the maintenance of redox homeostasis. However, the expression pattern and function of Nrf2 in the maturation of DCs in the glioma-infiltrated microenvironment remain unrevealed. Our study aims to investigate the roles of Nrf2 in glioma cell-tamed DCs and their impact on the downstream T cell proliferation and cytotoxicity to glioma cells. It was showed that the inducible maturation of DCs was significantly suppressed after stimulation with tumor-conditioned medium (TCM) prepared from glioma cells (LN-18 and U118MG), as suggested by the decreased CD80, CD86 and IL-12 p70 expression and higher levels of IL-10 than the normal astrocyte medium treated DCs...
August 4, 2017: Experimental Cell Research
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