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https://www.readbyqxmd.com/read/29339375/tusc2-immunogene-synergizes-with-anti-pd1-through-enhanced-proliferation-and-infiltration-of-natural-killer-cells-in-syngeneic-kras-mutant-mouse-lung-cancer-models
#1
Ismail M Meraz, Mourad Majidi, Xiaobo Cao, Heather Lin, Lerong Li, Jing Wang, Veerabhadran Baladandayuthapani, David Rice, Boris Sepesi, Lin Ji, Jack A Roth
Expression of the multikinase inhibitor encoded by tumor suppressor gene TUSC2 (also known as FUS1) is lost or decreased in non-small cell lung carcinoma (NSCLC). TUSC2 delivered systemically by nanovesicles has mediated tumor regression in clinical trials. Because of the role of TUSC2 in regulating immune cells, we assessed TUSC2 efficacy on antitumor immune responses alone and in combination with anti-PD-1 in two Kras-mutant syngeneic mouse lung cancer models. TUSC2 alone significantly reduced tumor growth and prolonged survival compared with anti-PD-1...
January 16, 2018: Cancer Immunology Research
https://www.readbyqxmd.com/read/29308327/enhancement-of-antibody-dependent-cellular-cytotoxicity-of-cetuximab-by-a-chimeric-protein-encompassing-interleukin-15
#2
Maria Carmen Ochoa, Luna Minute, Ascensión López, Elisabeth Pérez-Ruiz, Celia Gomar, Marcos Vasquez, Susana Inoges, Iñaki Etxeberria, Inmaculada Rodriguez, Saray Garasa, Jan-Peter Andreas Mayer, Peter Wirtz, Ignacio Melero, Pedro Berraondo
Enhancement of antibody-dependent cellular cytotoxicity (ADCC) may potentiate the antitumor efficacy of tumor-targeted monoclonal antibodies. Increasing the numbers and antitumor activity of NK cells is a promising strategy to maximize the ADCC of standard-of-care tumor-targeted antibodies. For this purpose, we have preclinically tested a recombinant chimeric protein encompassing the sushi domain of the IL15Rα, IL-15, and apolipoprotein A-I (Sushi-IL15-Apo) as produced in CHO cells. The size-exclusion purified monomeric fraction of this chimeric protein was stable and retained the IL-15 and the sushi domain bioactivity as measured by CTLL-2 and Mo-7e cell proliferation and STAT5 phosphorylation in freshly isolated human NK and CD8+ T cells...
2018: Oncoimmunology
https://www.readbyqxmd.com/read/29224228/newcastle-disease-virus-ndv-co-expressing-il7-and-il15-modified-tumor-cells-as-a-vaccine-for-cancer-immunotherapy
#3
Xiaojing Xu, Qing Sun, Yu Mei, Yonghao Liu, Lixiang Zhao
IL15 and IL7 are two cytokines essential for T cell development and homeostasis. In order to improve the antitumor activity by Newcastle Disease Virus (NDV)-modified tumor vaccine, we generated a recombinant NDV co-expressing IL15 and IL7 (LX/IL(15+7)) by incorporation of a 2A self-processing peptide into IL15 and IL7 using reverse genetics. B16 cells infected with LX/IL(15+7) expressed both IL15 and IL7 stably. The cytotoxicity assay showed that murine melanoma cells modified with LX/IL(15+7) could significantly enhance the antitumor immune response in vitro...
December 10, 2017: Cancer Science
https://www.readbyqxmd.com/read/29168191/genetic-variants-in-il15-promoter-affect-transcription-activity-and-intramuscular-fat-deposition-in-longissimus-dorsi-muscle-of-pigs
#4
D He, Z Jiang, Y Tian, H Han, M Xia, W Wei, L Zhang, J Chen
Intramuscular fat (IMF) content is a key aspect of pork quality. Elucidation of intramuscular adipocyte regulation mechanisms is important for improving IMF content. Intramuscular adipocytes are dispersed among muscle fibers, so they are inclined to be affected by muscle-derived factors. Interleukin-15 is a major muscle-secreted factor. In this study, the genetic and physiological impacts of IL15 on adipogenesis is investigated. The promoter region of IL15 was scanned by comparative sequencing using two DNA pools of high- and low-IMF individuals...
November 22, 2017: Animal Genetics
https://www.readbyqxmd.com/read/29164679/novel-antioxidant-and-anti-inflammatory-peptides-from-the-siamese-crocodile-crocodylus-siamensis-hemoglobin-hydrolysate
#5
Jiraporn Lueangsakulthai, Santi Phosri, Tinnakorn Theansungnoen, Nisachon Jangpromma, Theeranan Temsiripong, John E Mckendrick, Watcharee Khunkitti, Sompong Klaynongsruang
Novel antioxidant and anti-inflammatory peptides were isolated from hydrolysates of Siamese crocodile (Crocodylus siamensis) hemoglobin. Crocodylus siamensis hemoglobin hydrolysates (CHHs) were obtained by pepsin digestion at different incubation times (2, 4, 6 and 8 H) at 37 °C and subjected to antioxidant and anti-inflammatory activity assessment. CHH obtained by 2-H hydrolysis (2H-CHH) showed the highest anti-inflammatory activity with respect to decreasing nitric oxide (NO) production, while the strongest antioxidant activity was found for 6-H hydrolysis (6H-CHH) against nitric oxide radicals...
November 22, 2017: Biotechnology and Applied Biochemistry
https://www.readbyqxmd.com/read/29128220/identification-of-potential-embryokines-in-the-bovine-reproductive-tract
#6
P Tríbulo, L G B Siqueira, L J Oliveira, T Scheffler, P J Hansen
Knowledge of the molecules used by the maternal reproductive tract to regulate development of the preimplantation embryo is largely incomplete. The goal of the present experiment was to identify candidates for this function. The approach was to assess expression patterns in the endometrium and oviduct of 93 genes encoding for hormones, growth factors, chemokines, cytokines, and WNT-related molecules. Results show that all of the genes were expressed in the reproductive tract. Expression in oviduct was affected by day of the estrous cycle for 21 genes with 11 genes having highest expression at estrus (CCL21, CTGF, CXCL10, CXCL16, DKK3, FGF10, IL18, IL33, IL34, PGF, and SFRP2), one gene at d 3 (WNT4), 8 at d 5 (BMP7, HGF, IL6, SFRP1, TGFB1, WIF1, WNT2, and WNT5A), and one at d 7 (IK)...
November 8, 2017: Journal of Dairy Science
https://www.readbyqxmd.com/read/29109792/mir-205-yap1-in-activated-fibroblasts-of-breast-tumor-promotes-vegf-independent-angiogenesis-through-stat3-signaling
#7
Yan-E Du, Gang Tu, Guanglun Yang, Genyou Li, Dan Yang, Lei Lang, Lei Xi, Kexin Sun, Yanlin Chen, Kunxian Shu, Huadong Liao, Manran Liu, Yixuan Hou
Tumor microenvironment contributes to tumor angiogenesis. However, the role of the activated cancer associated-fibroblasts (CAFs) in angiogenesis is still unclear. Here we report that miR-205/YAP1 signaling in the activated stromal fibroblasts plays a critical role in VEGF-independent angiogenesis in breast tumor. Methods: miR-205 expression was assessed by quantitative real-time polymerase chain reaction (qRT-PCR); YAP1 expression by qRT-PCR, western blotting and immunohistochemistry; IL11 and IL15 expression by qRT-PCR, western blotting and ELISA...
2017: Theranostics
https://www.readbyqxmd.com/read/29078283/humanized-mouse-model-supports-development-function-and-tissue-residency-of-human-natural-killer-cells
#8
Dietmar Herndler-Brandstetter, Liang Shan, Yi Yao, Carmen Stecher, Valerie Plajer, Melanie Lietzenmayer, Till Strowig, Marcel R de Zoete, Noah W Palm, Jie Chen, Catherine A Blish, Davor Frleta, Cagan Gurer, Lynn E Macdonald, Andrew J Murphy, George D Yancopoulos, Ruth R Montgomery, Richard A Flavell
Immunodeficient mice reconstituted with a human immune system represent a promising tool for translational research as they may allow modeling and therapy of human diseases in vivo. However, insufficient development and function of human natural killer (NK) cells and T cell subsets limit the applicability of humanized mice for studying cancer biology and therapy. Here, we describe a human interleukin 15 (IL15) and human signal regulatory protein alpha (SIRPA) knock-in mouse on a Rag2-/- Il2rg-/- background (SRG-15)...
November 7, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29025069/wnk-lysine-deficient-protein-kinase-1-regulates-human-endometrial-stromal-cell-decidualization-proliferation-and-migration-in-part-through-mitogen-activated-protein-kinase-7
#9
Nyssa R Adams, Yasmin M Vasquez, Qianxing Mo, William Gibbons, Ertug Kovanci, Francesco J DeMayo
The differentiation of endometrial stromal cells into decidual cells, termed decidualization, is an integral step in the establishment of pregnancy. The mitogen-activated protein kinase homolog, WNK lysine deficient protein kinase 1 (WNK1), is activated downstream of epidermal growth factor receptor during decidualization. Primary human endometrial stromal cells (HESCs) were subjected to small interfering RNA knockdown of WNK1 followed by in vitro decidualization. This abrogated expression of the decidual marker genes, insulin like growth factor binding protein 1 (IGFBP1) and prolactin (PRL), and prevented adoption of decidual cell morphology...
September 1, 2017: Biology of Reproduction
https://www.readbyqxmd.com/read/28861771/recombinant-rabies-virus-expressing-il-15-enhances-immunogenicity-through-promoting-the-activation-of-dendritic-cells-in-mice
#10
Tiange Chen, Yajing Zhang, Zhao Wang, Jie Yang, Mingming Li, Kunlun Wang, Min Cui, Zhen F Fu, Ling Zhao, Ming Zhou
Rabies remains a public health threat that kills approximately 59,000 people worldwide each year, most of which are from the developing countries of Africa and Asia where dog rabies are endemic. Therefore, developing an affordable and efficacious vaccine is crucial for rabies control in these countries. Interleukin (IL)-15, an immunoregulatory cytokine, is a pluripotent molecule with therapeutic potential, which targets many cell types and links the innate and adaptive immune system. In this study, IL-15 gene was cloned and inserted into the genome of a recombinant rabies virus (RABV) strain LBNSE (designated as LBNSE-IL15), and the effect of over-expression of IL-15 on the immunogenicity of RABV was investigated...
August 2017: Virologica Sinica
https://www.readbyqxmd.com/read/28842470/il15-infusion-of-cancer-patients-expands-the-subpopulation-of-cytotoxic-cd56-bright-nk-cells-and-increases-nk-cell-cytokine-release-capabilities
#11
Sigrid Dubois, Kevin C Conlon, Jürgen R Müller, Jennifer Hsu-Albert, Nancy Beltran, Bonita R Bryant, Thomas A Waldmann
The cytokine IL15 is required for survival and activation of natural killer (NK) cells as well as expansion of NK-cell populations. Here, we compare the effects of continuous IL15 infusions on NK-cell subpopulations in cancer patients. Infusions affected the CD56(bright) NK-cell subpopulation in that the expansion rates exceeded those of CD56(dim) NK-cell populations with a 350-fold increase in their total cell numbers compared with 20-fold expansion for the CD56(dim) subset. CD56(bright) NK cells responded with increased cytokine release to various stimuli, as expected given their immunoregulatory functions...
August 25, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28827115/effect-of-il15-rs10833-and-scarb1-rs10846744-on-virologic-responses-in-chronic-hepatitis-c-patients-treated-with-pegylated-interferon-%C3%AE-and-ribavirin
#12
Sahar Sadeghi, Mehdi Davari, Esmaeil Asli, Safoora Gharibzadeh, Farzam Vaziri, Fatemeh Rahimi Jamnani, Abolfazl Fateh, Seyed Davar Siadat
The scavenger receptor type B class I (SCARBI) is known to be involved in the entry of hepatitis C virus (HCV) into the host, while interleukin-15 (IL15) is an important cytokine in both the innate and acquired immune responses against HCV infection. We investigated the association of IL15 rs10833 or SCARB1 rs10846744 polymorphisms with treatment responses in patients with chronic HCV (CHC). SCARB1 rs10846744 and IL15 rs10833 were identified in 365 treatment-naïve CHC patients through genotyping by TaqMan® Real-Time PCR and PCR-restriction fragment length polymorphism (RFLP), respectively...
September 30, 2017: Gene
https://www.readbyqxmd.com/read/28811289/primary-tumors-limit-metastasis-formation-through-induction-of-il15-mediated-crosstalk-between-patrolling-monocytes-and-nk-cells
#13
Hiroshi Kubo, Sofia Mensurado, Natacha Goncalves-Sousa, Karine Serre, Bruno Silva-Santos
Metastases are responsible for the vast majority of cancer-related deaths. Although tumor cells can become invasive early during cancer progression, metastases formation typically occurs as a late event. How the immune response to primary tumors may dictate this outcome remains poorly understood, which hampers our capacity to manipulate it therapeutically. Here we used a two-step experimental model, based on the highly aggressive B16F10 melanoma, that temporally segregates the establishment of primary tumors (subcutaneously) and the formation of lung metastases (from intravenous injection)...
August 15, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28807496/cd4-effector-t-cell-differentiation-is-controlled-by-il-15-that-is-expressed-and-presented-in-trans
#14
Adam T Waickman, Davinna L Ligons, SuJin Hwang, Joo-Young Park, Vanja Lazarevic, Noriko Sato, Changwan Hong, Jung-Hyun Park
T cells are both producers and consumers of cytokines, and autocrine cytokine signaling plays a critical role in T cell immunity. IL-15 is a homeostatic cytokine for T cells that also controls inflammatory immune responses. An autocrine role of T cell-derived IL-15, however, remains unclear. Here we examined IL-15 expression and signaling upon effector T cell differentiation in mice, and, surprisingly, found that CD4 T cells did not express IL-15. CD4 T cells lacked Il15 gene reporter activity, did not contain IL-15 transcripts, and did not produce IL-15Rα, the proprietary IL-15 receptor required for IL-15 trans-presentation...
November 2017: Cytokine
https://www.readbyqxmd.com/read/28738233/association-of-the-il-15-and-il-15r%C3%AE-genes-with-celiac-disease
#15
Celia Escudero-Hernández, Leticia Plaza-Izurieta, José A Garrote, José Ramón Bilbao, Eduardo Arranz
Celiac disease is a chronic autoimmune condition triggered by dietary gluten in genetically predisposed individuals and the treatment is a strict gluten-free diet. The major predisposing genes are HLA-DQA1 and HLA-DQB1, but these are not sufficient for disease development. One of the candidate genes worth studying is interleukin (IL)-15 gene, together with its specific receptor, IL-15Rα, as they participate in promoting lymphocyte signaling and survival, and the establishment of appropriate conditions for villous atrophy, then acting as key players in the immunopathogenesis of CD...
July 21, 2017: Cytokine
https://www.readbyqxmd.com/read/28670317/safeguarding-of-fetal-growth-by-mast-cells-and-natural-killer-cells-deficiency-of-one-is-counterbalanced-by-the-other
#16
Nicole Meyer, Katja Woidacki, Marcus Maurer, Ana Claudia Zenclussen
Uterine natural killer cells (uNKs) and mast cells (uMCs) are of crucial importance for spiral artery (SA) remodeling and placentation. Mice deficient for both NKs and MCs including uNKs and uMCs show markedly impaired SA remodeling and their fetuses are growth-retarded. In contrast, the absence of either NKs or MCs results in only minor impairment. This suggests that uNKs can compensate for the effects of uMCs on SA remodeling and vice versa. To test this hypothesis, we assessed uNK numbers in uMC-deficient mice as well as uMC numbers in uNK-depleted mice...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28651743/the-combination-of-nk-and-cd8-t-cells-with-ccl20-il15-armed-oncolytic-adenoviruses-enhances-the-growth-suppression-of-tert-positive-tumor-cells
#17
Jun-Feng Ye, Wen-Xi Qi, Ming-Yuan Liu, Yang Li
Adoptive immunotherapy and targeted gene therapy have been extensively used to eliminate tumor cells. The combination treatment is capable of efficiently generating an effective antitumor immune response and disrupting tumor-induced tolerance. Moreover, effective antitumor immune responses are dependent on coordinate interaction among various effector cells. This study focused on whether the combination of cytotoxic effector cell-based adoptive immunotherapy and CCL20/IL15-armed oncolytic adenoviruses could induce enhanced antitumor activity...
August 2017: Cellular Immunology
https://www.readbyqxmd.com/read/28637876/monocyte-derived-dendritic-cells-with-silenced-pd-1-ligands-and-transpresenting-interleukin-15-stimulate-strong-tumor-reactive-t-cell-expansion
#18
Johan M J Van den Bergh, Evelien L J M Smits, Zwi N Berneman, Tim J A Hutten, Hans De Reu, Viggo F I Van Tendeloo, Harry Dolstra, Eva Lion, Willemijn Hobo
Although allogeneic stem cell transplantation (allo-SCT) can elicit graft-versus-tumor (GVT) immunity, patients often relapse due to residual tumor cells. As essential orchestrators of the immune system, vaccination with dendritic cells (DC) is an appealing strategy to boost the GVT response. Nevertheless, durable clinical responses after DC vaccination are still limited, stressing the need to improve current DC vaccines. Aiming to empower DC potency, we engineered monocyte-derived DCs to deprive them of ligands for the immune checkpoint regulated by programmed death 1 (PD-1)...
August 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28602725/il15ra-is-required-for-osteoblast-function-and-bone-mineralization
#19
Emanuele Loro, Girish Ramaswamy, Abhishek Chandra, Wei-Ju Tseng, Manoj K Mishra, Eileen M Shore, Tejvir S Khurana
Interleukin-15 receptor alpha (IL15RA) is an important component of interleukin-15 (IL15) pro-inflammatory signaling. In addition, IL15 and IL15RA are present in the circulation and are detected in a variety of tissues where they influence physiological functions such as muscle contractility and overall metabolism. In the skeletal system, IL15RA was previously shown to be important for osteoclastogenesis. Little is known, however, about its role in osteoblast function and bone mineralization. In this study, we evaluated bone structural and mechanical properties of an Il15ra whole-body knockout mouse (Il15ra(-/-)) and used in vitro and bioinformatic analyses to understand the role IL15/IL15RA signaling on osteoblast function...
October 2017: Bone
https://www.readbyqxmd.com/read/28550091/transgenic-expression-of-il15-improves-antiglioma-activity-of-il13r%C3%AE-2-car-t-cells-but-results-in-antigen-loss-variants
#20
Giedre Krenciute, Brooke L Prinzing, Zhongzhen Yi, Meng-Fen Wu, Hao Liu, Gianpietro Dotti, Irina V Balyasnikova, Stephen Gottschalk
Glioblastoma (GBM) is the most aggressive primary brain tumor in adults and is virtually incurable with conventional therapies. Immunotherapy with T cells expressing GBM-specific chimeric antigen receptors (CAR) is an attractive approach to improve outcomes. Although CAR T cells targeting GBM antigens, such as IL13 receptor subunit α2 (IL13Rα2), HER2, and EGFR variant III (EGFRvIII), have had antitumor activity in preclinical models, early-phase clinical testing has demonstrated limited antiglioma activity...
July 2017: Cancer Immunology Research
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