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tumor induced immune suppression

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https://www.readbyqxmd.com/read/28231612/the-pro-inflammatory-cytokine-tnf-%C3%AE-inhibits-lymphatic-pumping-via-activation-of-the-nf-%C3%AE%C2%BAb-inos-signaling-pathway
#1
Yingxuan Chen, Sonia Rehal, Simon Roizes, Hai-Lei Zhu, William C Cole, Pierre-Yves von der Weid
OBJECTIVE: Mesenteric lymphatic vessels pumping, important to propel lymph and immune cells from the intestinal interstitium to the mesenteric lymph nodes, is compromised during intestinal inflammation. The objective of this study was to test the hypothesis that the pro-inflammatory cytokine tumor necrosis factor alpha (TNF-α), is a significant contributor to the inflammation-induced lymphatic contractile dysfunction, and to determine its mode of action. METHODS: Contractile parameters were obtained form isolated rat mesenteric lymphatic vessels mounted on a pressure myograph after 24-h incubation with or without TNF-α...
February 23, 2017: Microcirculation: the Official Journal of the Microcirculatory Society, Inc
https://www.readbyqxmd.com/read/28230260/elevation-of-sharpin-protein-levels-in-prostate-adenocarcinomas-promotes-metastasis-and-impairs-patient-survivals
#2
Hai Huang, Tao Du, Yiming Zhang, Yiming Lai, Kaiwen Li, Xinxing Fan, Dingjun Zhu, Tianxin Lin, Kewei Xu, Jian Huang, Leyuan Liu, Zhenghui Guo
BACKGROUND: SHARPIN, SHANK-associated RH domain interacting protein, associates with a linear ubiquitin chain assembly complex (LUBAC) to regulate inflammation and immunity. It has been reported that SHARPIN is highly expressed in several human tumors including ovarian cancer and liver cancer. We found that SHARPIN is also highly expressed in prostate cancer cell lines of DU145, LNCAP, and PC-3. Suppression of SHARPIN caused an inhibition of NF-κB signal and decreases in tumorigenesis of cultured cells in NOD/SCID mouse model...
February 23, 2017: Prostate
https://www.readbyqxmd.com/read/28228558/the-ribosomal-protein-s19-suppresses-antitumor-immune-responses-via-the-complement-c5a-receptor-1
#3
Maciej M Markiewski, Surya Kumari Vadrevu, Sharad K Sharma, Navin Kumar Chintala, Shanawaz Ghouse, Jun-Hung Cho, David P Fairlie, Yvonne Paterson, Aristotelis Astrinidis, Magdalena Karbowniczek
Relatively little is known about factors that initiate immunosuppression in tumors and act at the interface between tumor cells and host cells. In this article, we report novel immunosuppressive properties of the ribosomal protein S19 (RPS19), which is upregulated in human breast and ovarian cancer cells and released from apoptotic tumor cells, whereupon it interacts with the complement C5a receptor 1 expressed on tumor infiltrating myeloid-derived suppressor cells. This interaction promotes tumor growth by facilitating recruitment of these cells to tumors...
February 22, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28224212/upregulation-of-thioredoxin-1-in-activated-human-nk-cells-confers-increased-tolerance-to-oxidative-stress
#4
Kousaku Mimura, Ley-Fang Kua, Noriko Shimasaki, Kensuke Shiraishi, Shotaro Nakajima, Lim Kee Siang, Asim Shabbir, Jimmy So, Wei-Peng Yong, Koji Kono
Adoptive transfer of immune cells, such as T lymphocytes and NK cells, has potential to control cancer growth. However, this can be counteracted by immune escape mechanisms within the tumor microenvironment, including those mediated by reactive oxygen species (ROS). Here, we determined the levels of anti-oxidant molecules in NK cells and their capacity to overcome ROS-induced immune suppression. We investigated the effect of H2O2 on resting NK cells, IL-2-activated NK cells and NK cells expanded by coculture with the K562 leukemia cell line genetically modified to express membrane-bound IL-15 and 4-1BB ligand (K562-mb15-41BBL)...
February 21, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28224211/mechanisms-overseeing-myeloid-derived-suppressor-cell-production-in-neoplastic-disease
#5
REVIEW
Colleen S Netherby, Scott I Abrams
Perturbations in myeloid cell differentiation are common in neoplasia, culminating in immature populations known as myeloid-derived suppressor cells (MDSCs). MDSCs favor tumor progression due to their ability to suppress host immunity or promote invasion and metastasis. They are thought to originate from the bone marrow as a result of exposure to stromal- or circulating tumor-derived factors (TDFs). Although great interest has been placed on understanding how MDSCs function, less is known regarding how MDSCs develop at a transcriptional level...
February 21, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28222746/c-terminal-region-of-apoptin-affects-chicken-anemia-virus-replication-and-virulence
#6
REVIEW
Yongqiang Wang, Xiuqing Song, Honglei Gao, Xiaoyan Wang, Yonghao Hu, Yulong Gao, Xiaole Qi, Liting Qin, Huan Lin, Li Gao, Shuai Yao, Chunyan Han, Xiaomei Wang, Hualan Chen
BACKGROUND: Chicken anemia virus (CAV) causes anemia and immune suppression, which are important diseases in the poultry industry. CAV VP3, also referred as 'apoptin', has been shown to selectively kill tumor cells, raising great hopes for its utilization as an anticancer therapy. The ability of apoptin to induce apoptosis is closely related to its nuclear localization. The C-terminal region of apoptin contains a bipartite nuclear localization signals (NLS), and a nuclear export signal (NES) is located between the arms of the NLS...
February 21, 2017: Virology Journal
https://www.readbyqxmd.com/read/28220904/recent-advances-in-occupational-and-environmental-health-hazards-of-workers-exposed-to-gasoline-compounds
#7
REVIEW
Christopher E Ekpenyong, Asuquo E Asuquo
The impact of health and environmental hazards, associated with the constituents of gasoline, on occupationally exposed workers has been recorded over the past few decades. However, the scientific literature on their pathogenic potential remains incomplete, which could affect the current understanding of the associated health risks. This review provides current information based on recently improved research techniques to evaluate gasoline toxicity profiles for humans. Our current knowledge provides insight into the intricate mechanism of gasoline-induced adverse effects, including the formation of reactive metabolites via bio-activation and subsequent generation of reactive oxygen species (ROS) and oxidative stress, which are involved in multiple mechanisms that are central to the aetiology of gasoline-induced toxicity...
February 21, 2017: International Journal of Occupational Medicine and Environmental Health
https://www.readbyqxmd.com/read/28220341/adenovirus-mediated-small-interfering-rna-targeting-tak1-ameliorates-joint-inflammation-with-collagen-induced-arthritis-in-mice
#8
Xinjing Luo, Yongfeng Chen, Guoju Lv, Zhidong Zhou, Jie Chen, Xuanrong Mo, Jiangwen Xie
Transforming growth factor β-activated kinase-1 (TAK1) is a key upstream kinase in cell signaling during inflammation, which regulates the expression of inflammatory mediators. Small interfering RNA (siRNA) against TAK1 offers promise as a potential therapeutic strategy in immune-mediated inflammatory disorder including rheumatoid arthritis. Here, we are to evaluate the therapeutic effects of intra-articular administration of adenoviral-mediated siRNA against TAK1 (ad-siRNA-TAK1) on collagen-induced arthritis (CIA) in mice...
February 21, 2017: Inflammation
https://www.readbyqxmd.com/read/28218497/chemotherapy-induces-tumor-immune-evasion-by-upregulation-of-programmed-cell-death-ligand%C3%A2-1-expression-in-bone-marrow-stromal-cells
#9
Mengqi Yang, Panpan Liu, Kefeng Wang, Christophe Glorieux, Yumin Hu, Shijun Wen, Wenqi Jiang, Peng Huang
Programmed cell death ligand 1 (PD-L1) is a negative regulator of the immune response that enables tumor cells to escape T-cell immunity. Although PD-L1 expression in cancer cells has been extensively studied, the expression of PD-L1 in stromal cells and its clinical significance remain largely unknown. Here, we show that bone marrow stromal cells express a low level of PD-L1 and that this molecule is significantly upregulated by key drugs used in the treatment of lymphoma at clinically relevant concentrations...
December 28, 2016: Molecular Oncology
https://www.readbyqxmd.com/read/28216374/yin-yang-effect-of-tumor-infiltrating-b-cells-in-breast-cancer-from-mechanism-to-immunotherapy
#10
Zhigang Zhang, Ying Zhu, Zhen Wang, Ting Zhang, Pin Wu, Jian Huang
Breast cancer cells secrete chemokines, such as CXCL13, and antigens or express high endothelial venules, attracting B cells to infiltrate into the tumor microenvironment and play a "yin-yang" effect. They not only enhance the anti-tumor immune effect via secreting antibodies and influencing the Fas/FasL, CXCR4/CXCL12 and perforin pathways but they also promote the tumor to form a suppressive milieu by producing immunomodulatory factors and cytokines or using cell-to-cell education to induce the generation of Tregs or myeloid-derived suppressor cells (MDSCs)...
February 16, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28214928/dendritic-cell-rehab-new-strategies-to-unleash-therapeutic-immunity-in-ovarian-cancer
#11
REVIEW
Chang-Suk Chae, Eli Teran-Cabanillas, Juan R Cubillos-Ruiz
Immune-based therapies that induce remarkable and durable responses against melanoma and lung cancer have unfortunately demonstrated limited success in ovarian cancer patients. This is likely due to the exceptional immunoregulatory nature of ovarian tumors, which employ numerous strategies to effectively suppress anti-tumor immunity. Here, we summarize a decade of research indicating that ovarian cancers possess an exquisite capacity to subvert the activity of host dendritic cells (DCs) as a key mechanism to impede the development and maintenance of protective T cell-based immune responses...
February 18, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28212753/the-trail-induced-cancer-secretome-promotes-a-tumor-supportive-immune-microenvironment-via-ccr2
#12
Torsten Hartwig, Antonella Montinaro, Silvia von Karstedt, Alexandra Sevko, Silvia Surinova, Ankur Chakravarthy, Lucia Taraborrelli, Peter Draber, Elodie Lafont, Frederick Arce Vargas, Mona A El-Bahrawy, Sergio A Quezada, Henning Walczak
Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is known for specifically killing cancer cells, whereas in resistant cancers, TRAIL/TRAIL-R can promote metastasis via Rac1 and PI3K. It remains unknown, however, whether and to what extent TRAIL/TRAIL-R signaling in cancer cells can affect the immune microenvironment. Here we show that TRAIL-triggered cytokine secretion from TRAIL-resistant cancer cells is FADD dependent and identify the TRAIL-induced secretome to drive monocyte polarization to myeloid-derived suppressor cells (MDSCs) and M2-like macrophages...
February 16, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28202625/gut-microbiota-promotes-obesity-associated-liver-cancer-through-pge2-mediated-suppression-of-antitumor-immunity
#13
Tze Mun Loo, Fumitaka Kamachi, Yoshihiro Watanabe, Shin Yoshimoto, Hiroaki Kanda, Yuriko Arai, Yaeko Nakajima-Takagi, Atsushi Iwama, Tomoaki Koga, Yukihiko Sugimoto, Takayuki Ozawa, Masaru Nakamura, Miho Kumagai, Koichi Watashi, Makoto M Taketo, Tomohiro Aoki, Shuh Narumiya, Masanobu Oshima, Makoto Arita, Eiji Hara, Naoko Ohtani
Obesity increases the risk of cancers, including hepatocellular carcinomas (HCCs). However, the precise molecular mechanisms through which obesity promotes HCC development are still unclear. Recent studies have shown that gut microbiota may influence liver diseases by transferring its metabolites and components. Here, we show that the hepatic translocation of obesity-induced lipoteichoic acid (LTA), a Gram positive gut microbial component, promotes HCC development by creating a tumor-promoting microenvironment...
February 15, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28202353/the-potential-clinical-promise-of-multimodality-metronomic-chemotherapy-revealed-by-preclinical-studies-of-metastatic-disease
#14
Robert S Kerbel, Yuval Shaked
We present a rationale for further clinical development and assessment of metronomic chemotherapy on the basis of unexpected results obtained in translational mouse models of cancer involving treatment of advanced metastatic disease. Historically, mouse cancer therapy models have been dominated by treating established primary tumors or early stage low volume microscopic disease. Treatment of primary tumors is also almost always the case when using genetically engineered mouse models (GEMMS) of cancer or patient-derived xenografts (PDXs)...
February 12, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28199142/dc-stamp-is-an-osteoclast-fusogen-engaged-in-periodontal-bone-resorption
#15
W Wisitrasameewong, M Kajiya, A Movila, S Rittling, T Ishii, M Suzuki, S Matsuda, Y Mazda, M R Torruella, M M Azuma, K Egashira, M O Freire, H Sasaki, C Y Wang, X Han, M A Taubman, T Kawai
Dendritic cell-specific transmembrane protein (DC-STAMP) plays a key role in the induction of osteoclast (OC) cell fusion, as well as DC-mediated immune regulation. While DC-STAMP gene expression is upregulated in the gingival tissue with periodontitis, its pathophysiological roles in periodontitis remain unclear. To evaluate the effects of DC-STAMP in periodontitis, anti-DC-STAMP-monoclonal antibody (mAb) was tested in a mouse model of ligature-induced periodontitis ( n = 6-7/group) where Pasteurella pneumotropica ( Pp)-reactive immune response activated T cells to produce receptor activator of nuclear factor kappa-B ligand (RANKL), which, in turn, promotes the periodontal bone loss via upregulation of osteoclastogenesis...
February 1, 2017: Journal of Dental Research
https://www.readbyqxmd.com/read/28197388/inhibition-of-tumor-growth-and-metastasis-by-emmprin-multiple-antigenic-peptide-map-vaccination-is-mediated-by-immune-modulation
#16
Elina Simanovich, Vera Brod, Maya M Rahat, Ella Drazdov, Miriam Walter, Jivan Shakya, Michal A Rahat
Previously, we have identified a new epitope in EMMPRIN, a multifunctional protein that mediates tumor cell-macrophage interactions and induces both MMP-9 and VEGF. Here, we synthesized this epitope as an octa-branched multiple antigenic peptide (MAP) to vaccinate mice implanted with subcutaneous syngeneic colon (CT26), prostate (TRAMP-C2) or renal (RENCA) cell line carcinomas. Vaccination inhibited, and sometimes regressed, tumor growth in a dose-dependent manner, reaching 94%, 71% and 72% inhibition, respectively, at a 50 μg dose (p < 0...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28197367/targeting-ewing-sarcoma-with-activated-and-gd2-specific-chimeric-antigen-receptor-engineered-human-nk-cells-induces-upregulation-of-immune-inhibitory-hla-g
#17
Sareetha Kailayangiri, Bianca Altvater, Christian Spurny, Silke Jamitzky, Sonja Schelhaas, Andreas H Jacobs, Constanze Wiek, Katharina Roellecke, Helmut Hanenberg, Wolfgang Hartmann, Heinz Wiendl, Susann Pankratz, Jutta Meltzer, Nicole Farwick, Lea Greune, Maike Fluegge, Claudia Rossig
Activated and in vitro expanded natural killer (NK) cells have substantial cytotoxicity against many tumor cells, but their in vivo efficacy to eliminate solid cancers is limited. Here, we used chimeric antigen receptors (CARs) to enhance the activity of NK cells against Ewing sarcomas (EwS) in a tumor antigen-specific manner. Expression of CARs directed against the ganglioside antigen GD2 in activated NK cells increased their responses to GD2+ allogeneic EwS cells in vitro and overcame resistance of individual cell lines to NK cell lysis...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28197363/small-gtpase-rbj-promotes-cancer-progression-by-mobilizing-mdscs-via-il-6
#18
Qiuyan Liu, Ha Zhu, Chaoxiong Zhang, Taoyong Chen, Xuetao Cao
RBJ has been identified to be dysregulated in gastrointestinal cancer and promotes tumorigenesis and progression by mediating nuclear accumulation of active MEK1/2 and sustained activation of ERK1/2. Considering that nuclear accumulation and constitutive activation of MEK/ERK not only promotes tumor progression directly, but also induces chronic inflammation, we wonder whether and how RBJ impairs host immune-surveillance via chronic inflammation and consequently supports tumor progression. Here, we report that higher expression of RBJ in human breast cancer tissue has been significantly correlated with poorer prognosis in breast cancer patients...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28196531/enhancing-circadian-clock-function-in-cancer-cells-inhibits-tumor-growth
#19
Silke Kiessling, Lou Beaulieu-Laroche, Ian D Blum, Dominic Landgraf, David K Welsh, Kai-Florian Storch, Nathalie Labrecque, Nicolas Cermakian
BACKGROUND: Circadian clocks control cell cycle factors, and circadian disruption promotes cancer. To address whether enhancing circadian rhythmicity in tumor cells affects cell cycle progression and reduces proliferation, we compared growth and cell cycle events of B16 melanoma cells and tumors with either a functional or dysfunctional clock. RESULTS: We found that clock genes were suppressed in B16 cells and tumors, but treatments inducing circadian rhythmicity, such as dexamethasone, forskolin and heat shock, triggered rhythmic clock and cell cycle gene expression, which resulted in fewer cells in S phase and more in G1 phase...
February 14, 2017: BMC Biology
https://www.readbyqxmd.com/read/28195314/reversal-of-tumor-acidosis-by-systemic-buffering-reactivates-nk-cells-to-express-ifn-%C3%AE-and-induces-nk-cell-dependent-lymphoma-control-without-other-immunotherapies
#20
Johann Pötzl, David Roser, Lorenz Bankel, Nadine Hömberg, Albert Geishauser, Christoph D Brenner, Michael Weigand, Martin Röcken, Ralph Mocikat
Like other immune cells, natural killer (NK) cells show impaired effector functions in the microenvironment of tumors, but little is known on the underlying mechanisms. Since lactate acidosis, a hallmark of malignant tissue, was shown to contribute to suppression of effective antitumor immune responses, we investigated the impact of tissue pH and lactate concentration on NK-cell functions in an aggressive model of endogenously arising B-cell lymphoma. The progressive loss of IFN-γ production by NK cells observed during development of this disease could be ascribed to decreased pH values and lactate accumulation in the microenvironment of growing tumors...
February 13, 2017: International Journal of Cancer. Journal International du Cancer
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