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https://www.readbyqxmd.com/read/28439087/3d-microfluidic-model-for-evaluating-immunotherapy-efficacy-by-tracking-dendritic-cell-behaviour-toward-tumor-cells
#1
Stefania Parlato, Adele De Ninno, Rosa Molfetta, Elena Toschi, Debora Salerno, Arianna Mencattini, Giulia Romagnoli, Alessandra Fragale, Lorenzo Roccazzello, Maria Buoncervello, Irene Canini, Enrico Bentivegna, Mario Falchi, Francesca Romana Bertani, Annamaria Gerardino, Eugenio Martinelli, Corrado Natale, Rossella Paolini, Luca Businaro, Lucia Gabriele
Immunotherapy efficacy relies on the crosstalk within the tumor microenvironment between cancer and dendritic cells (DCs) resulting in the induction of a potent and effective antitumor response. DCs have the specific role of recognizing cancer cells, taking up tumor antigens (Ags) and then migrating to lymph nodes for Ag (cross)-presentation to naïve T cells. Interferon-α-conditioned DCs (IFN-DCs) exhibit marked phagocytic activity and the special ability of inducing Ag-specific T-cell response. Here, we have developed a novel microfluidic platform recreating tightly interconnected cancer and immune systems with specific 3D environmental properties, for tracking human DC behaviour toward tumor cells...
April 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28436963/a-sting-activating-nanovaccine-for-cancer-immunotherapy
#2
Min Luo, Hua Wang, Zhaohui Wang, Haocheng Cai, Zhigang Lu, Yang Li, Mingjian Du, Gang Huang, Chensu Wang, Xiang Chen, Matthew R Porembka, Jayanthi Lea, Arthur E Frankel, Yang-Xin Fu, Zhijian J Chen, Jinming Gao
The generation of tumour-specific T cells is critically important for cancer immunotherapy. A major challenge in achieving a robust T-cell response is the spatiotemporal orchestration of antigen cross-presentation in antigen-presenting cells with innate stimulation. Here, we report a minimalist nanovaccine, comprising a simple physical mixture of an antigen and a synthetic polymeric nanoparticle, PC7A NP, which generates a strong cytotoxic T-cell response with low systemic cytokine expression. Mechanistically, the PC7A NP achieves efficient cytosolic delivery of tumour antigens to antigen-presenting cells in draining lymph nodes, leading to increased surface presentation while simultaneously activating type I interferon-stimulated genes...
April 24, 2017: Nature Nanotechnology
https://www.readbyqxmd.com/read/28432146/c1q-dependent-dendritic-cell-cross-presentation-of-in-vivo-formed-antigen-antibody-complexes
#3
Nataschja I Ho, Marcel G M Camps, Edwin F E de Haas, Leendert A Trouw, J Sjef Verbeek, Ferry Ossendorp
Dendritic cells (DCs) are specialized in Ag engulfment via a wide variety of uptake receptors on their cell surface. In the present study we investigated Ag uptake and presentation of in vivo-formed Ag-Ab complexes by i.v. injecting mice with Ag-specific Abs followed by the cognate Ag. We show by this natural Ab-mediated Ag targeting system that uptake by splenic APC subsets is severely hampered in mice lacking complement factor C1q (C1qa(-/-)). Moreover, no detectable Ag cross-presentation by CD8α(+) DCs from C1qa(-/-) mice was found...
April 21, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28432021/the-er-phagosome-connection-in-the-era-of-membrane-contact-sites
#4
REVIEW
Paula Nunes-Hasler, Nicolas Demaurex
Phagocytosis is an essential mechanism through which innate immune cells ingest foreign material that is either destroyed or used to generate and present antigens and initiate adaptive immune responses. While a role for the ER during phagosome biogenesis has been recognized, whether fusion with ER cisternae or vesicular derivatives occurs has been the source of much contention. Membrane contact sites (MCS) are tight appositions between ER membranes and various organelles that coordinate multiple functions including localized signalling, lipid transfer and trafficking...
April 18, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28414151/targeted-antigen-delivery-to-dendritic-cell-via-functionalized-alginate-nanoparticles-for-cancer-immunotherapy
#5
Chuangnian Zhang, Gaona Shi, Ju Zhang, Huijun Song, Jinfeng Niu, Shengbin Shi, Pingsheng Huang, Yanming Wang, Weiwei Wang, Chen Li, Deling Kong
The purpose of the present study was to identify an "easy-to-adopt" strategy to enhance immune responses using functionalized alginate (ALG) nanoparticles (MAN-ALG/ALG=OVA NPs), which were prepared by CaCl2 cross-linking of two different types of ALG. The mannose (MAN) modified ALG (MAN-ALG) was used for dendritic cell targeting. The other component, composed of ovalbumin (OVA), a model antigen, is conjugated to ALG (ALG=OVA) via pH sensitive Schiff base bond. Grafting of alginate was demonstrated by FT-IR and (1)H NMR, while the morphological structure, particle size, Zeta potential of MAN-ALG/ALG=OVA NPs were measured using TEM and DLS...
April 13, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28405513/tumor-sqstm1-p62-expression-and-t-cells-in-colorectal-cancer
#6
Keisuke Kosumi, Yohei Masugi, Juhong Yang, Zhi Rong Qian, Sun A Kim, Wanwan Li, Yan Shi, Annacarolina da Silva, Tsuyoshi Hamada, Li Liu, Mancang Gu, Tyler S Twombly, Yin Cao, David A Barbie, Katsuhiko Nosho, Hideo Baba, Wendy S Garrett, Jeffery A Meyerhardt, Edward L Giovannucci, Andrew T Chan, Charles S Fuchs, Shuji Ogino, Reiko Nishihara
Evidence suggests that activation of autophagy in neoplastic cells potentiates antitumor immunity through cross-presentation of tumor-associated antigens to T cells and release of immune mediators. The SQSTM1 (sequestosome 1, p62) protein is degraded by activated autophagy, and might enhance immune response to tumor cells. We hypothesized that tumor SQSTM1 expression level might be inversely associated with T-cell densities in colorectal carcinoma tissue. We evaluated tumor SQSTM1 expression by immunohistochemistry in 601 rectal and colon cancer cases within the Nurses' Health Study and Health Professionals Follow-up Study...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28405506/oral-delivery-of-tumor-microparticle-vaccines-activates-nod2-signaling-pathway-in-ileac-epithelium-rendering-potent-antitumor-t-cell-immunity
#7
Wenqian Dong, Huafeng Zhang, Xiaonan Yin, Yuying Liu, Degao Chen, Xiaoyu Liang, Xun Jin, Jiadi Lv, Jingwei Ma, Ke Tang, Zhuowei Hu, Xiaofeng Qin, Bo Huang
Exploiting gut mucosal immunity to design new antitumor vaccination strategy remains unexplored. Tumor cell-derived microparticles (T-MP) are natural biomaterials that are capable of delivering tumor antigens and innate signals to dendritic cells (DC) for tumor-specific T cell immunity. Here, we show that T-MPs by oral vaccination route effectively access and activate mucosal epithelium, leading to subsequent antitumor T cell responses. Oral vaccination of T-MPs generated potent inhibitory effect against the growth of B16 melanoma and CT26 colon cancer in mice, which required both T cell and DC activation...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28389664/the-tlr2-binding-neisserial-porin-porb-enhances-antigen-presenting-cell-trafficking-and-cross-presentation
#8
Michael L Reiser, Munir M Mosaheb, Christina Lisk, Andrew Platt, Lee M Wetzler
TOLL-like receptor (TLR) ligands activate both innate and adaptive immune cells, while modulating the cellular immune response. The outer membrane protein (OMP) from Neisseria meninigitidis, PorB, is a naturally occurring TLR2 ligand and functions as an adjuvant. Here, we demonstrate that PorB increases the level of OVA in the endo-/lysosomal cellular compartment of BMDCs, increases antigen presenting cell (APC) trafficking to draining lymph nodes, and enhances antigen cross-presentation. PorB is capable of mounting an antigen specific T cell response by efficiently stimulating antigen cross-presentation in vivo and in vitro assessed by BMDC OT-I cocultivation assays...
April 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28368960/ubiquitinated-proteins-isolated-from-tumor-cells-are-efficient-substrates-for-antigen-cross-presentation
#9
Guangjie Yu, Tarsem Moudgil, Zhihua Cui, Yongbin Mou, Lixin Wang, Bernard A Fox, Hong-Ming Hu
We have previously shown that inhibition of the proteasome causes defective ribosomal products to be shunted into autophagosomes and subsequently released from tumor cells as defective ribosomal products in Blebs (DRibbles). These DRibbles serve as an excellent source of antigens for cross-priming of tumor-specific T cells. Here, we examine the role of ubiquitinated proteins (Ub-proteins) in this pathway. Using purified Ub-proteins from tumor cells that express endogenous tumor-associated antigen or exogenous viral antigen, we tested the ability of these proteins to stimulate antigen-specific T-cell responses, by activation of monocyte-derived dendritic cells generated from human peripheral blood mononuclear cells...
March 31, 2017: Journal of Immunotherapy
https://www.readbyqxmd.com/read/28368498/the-antigen-presenting-potential-of-v%C3%AE-9v%C3%AE-2-t-cells-during-plasmodium-falciparum-blood-stage-infection
#10
Jennifer Howard, Séverine Loizon, Christopher J Tyler, Dorothée Duluc, Bernhard Moser, Matthieu Mechain, Alexandre Duvignaud, Denis Malvy, Marita Troye-Blomberg, Jean-Francois Moreau, Matthias Eberl, Odile Mercereau-Puijalon, Julie Déchanet-Merville, Charlotte Behr, Maria Mamani-Matsuda
During Plasmodium falciparum infections, erythrocyte-stage parasites inhibit dendritic cell maturation and function; compromising development of effective anti-malarial adaptive immunity. Human Vγ9Vδ2 T-cells can act in vitro as APCs and induce αβ T-cell activation. However, the relevance of this activity in pathophysiological contexts in vivo has remained elusive. Since Vγ9Vδ2 T-cells are activated during the early immune response against P.falciparum infection, we investigated whether they could contribute to the instruction of adaptive immune responses toward malaria parasites...
March 27, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28361233/rna-seq-analysis-for-transcriptome-profiling-in-response-to-classical-swine-fever-vaccination-in-indigenous-and-crossbred-pigs
#11
Shalu Kumari Pathak, Amit Kumar, G Bhuwana, Vaishali Sah, Vikramadiya Upmanyu, A K Tiwari, A P Sahoo, A R Sahoo, Sajjad A Wani, Manjit Panigrahi, N R Sahoo, Ravi Kumar
In present investigation, differential expression of transcriptome after classical swine fever (CSF) vaccination has been explored at the cellular level in crossbred and indigenous (desi) piglets. RNA Sequencing by Expectation-Maximization (RSEM) package was used to quantify gene expression from RNA Sequencing data, and differentially expressed genes (DEGs) were identified using EBSeq, DESeq2, and edgeR softwares. After analysis, 5222, 6037, and 6210 common DEGs were identified in indigenous post-vaccinated verses pre-vaccinated, crossbred post-vaccinated verses pre-vaccinated, and post-vaccinated crossbred verses indigenous pigs, respectively...
March 30, 2017: Functional & Integrative Genomics
https://www.readbyqxmd.com/read/28350860/uniquely-altered-transcripts-are-associated-with-immune-preservation-in-hiv-infection
#12
Michelle Zanoni, Ítalo Karmann Aventurato, James Hunter, Maria Cecilia Araripe Sucupira, Ricardo Sobhie Diaz
The mechanisms underlying host HIV control hold much promise in the search for a functional HIV cure. We investigated the host genomic signatures in elite controllers or rapid progressors following recent infection and the correlates of immune reconstitution during combination antiretroviral therapy. We characterized the HIV-specific longitudinal host transcriptional response of peripheral blood mononuclear cells from elite controllers, rapid progressors, immune responders and non-responders using a RT-qPCR array in a cohort of recently HIV-infected Brazilian individuals...
2017: PloS One
https://www.readbyqxmd.com/read/28345638/lectin-like-oxidized-low-density-lipoprotein-receptor-1-facilitates-metastasis-of-gastric-cancer-through-driving-epithelial-mesenchymal-transition-and-pi3k-akt-gsk3%C3%AE-activation
#13
Can Li, Jie Zhang, Hao Wu, Lili Li, Caiting Yang, Shushu Song, Peike Peng, Miaomiao Shao, Mingming Zhang, Junjie Zhao, Ran Zhao, Weicheng Wu, Yuanyuan Ruan, Lan Wang, Jianxin Gu
Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) is a pattern recognition receptor that plays a critical role in vascular diseases and host immune response. Recently, our research discovered that LOX-1 could facilitate the uptake of dying cells and cross-presentation of cellular antigen via binding with heat shock proteins, which have a close relationship with gastric neoplasia. Therefore, we speculated that LOX-1 may serve as an oncogene in gastric cancer (GC) development and progression. In this study, through immunohistochemistry staining assay and cancer-related databases, we found that LOX-1 expression was up-regulated in GC tissues and correlated with a poor prognosis in GC patients...
March 27, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28336379/synthetic-nanovaccines-for-immunotherapy
#14
Min Luo, Layla Z Samandi, Zhaohui Wang, Zhijian J Chen, Jinming Gao
Although vaccination is historically one of the most successful strategies for the prevention of infectious diseases, development of vaccines for cancer and many chronic infections, such as HIV, malaria, and tuberculosis, has remained a challenge. Strong and long-lasting antigen-specific T cell responses are critical for therapy of these diseases. A major challenge in achieving a robust CD8+ T cell response is the requirement of spatio-temporal orchestration of antigen cross-presentation in antigen-presenting cells with innate stimulation...
March 20, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28322289/poly-%C3%AE-glutamic-acid-chitosan-nanogel-greatly-enhances-the-efficacy-and-heterosubtypic-cross-reactivity-of-h1n1-pandemic-influenza-vaccine
#15
Jihyun Yang, Sang-Mu Shim, Thi Quyen Nguyen, Eun-Ha Kim, Kwang Kim, Yong Taik Lim, Moon-Hee Sung, Richard Webby, Haryoung Poo
In 2009, the global outbreak of an influenza pandemic emphasized the need for an effective vaccine adjuvant. In this study, we examined the efficacy of poly-γ-glutamic acid/chitosan (PC) nanogel as an adjuvant for the influenza vaccine. PC nanogel significantly enhanced antigen-specific cross-presentation and cytotoxic T lymphocyte (CTL) activity. Compared with alum, the protective efficacy of the pandemic H1N1 influenza (pH1N1) vaccine was substantially increased by PC nanogel, with increased hemagglutination-inhibition titers, CTL activity, and earlier virus clearance after homologous and heterosubtypic [A/Philippines/2/82 (H3N2)] virus challenges...
March 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28317931/recruitment-of-bone-marrow-cd11b-gr-1-cells-by-polymeric-nanoparticles-for-antigen-cross-presentation
#16
Ya-Wun Yang, Wen-Hui Luo
The objective of this study was to investigate the function of poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) on the activation of antigen-specific CD8(+) T cell responses via the CD11b(+)Gr(-)1(+) myeloid subpopulations in murine bone marrow (BM). PLGA NPs containing ovalbumin (OVA) were fabricated by the double-emulsion method. The CD11b(+)Gr-1(low)Ly-6C(high) and CD11b(+)Gr-1(high)Ly-6C(low) subsets from mice bone marrow were sorted and treated with the PLGA/OVA NPs, followed by co-culture with the carboxyfluorescein succinimidyl ester (CFSE)-labelled OT-I CD8(+) cells...
March 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28296410/a-light-responsive-nanoparticle-based-delivery-system-using-pheophorbide-a-graft-polyethylenimine-for-dendritic-cell-based-cancer-immunotherapy
#17
Chuangnian Zhang, Ju Zhang, Gaona Shi, Huijuan Song, Shengbin Shi, Xiuyuan Zhang, Pingsheng Huang, Zhihong Wang, Weiwei Wang, Chun Wang, Deling Kong, Chen Li
In this study, the photochemical internalization (PCI) technique was adopted in a nanoparticle-based antigen delivery system to enhance antigen-specific CD8(+) T cell immune response for cancer immunotherapy. Pheophorbide A, a hydrophobic photosensitizer, grafted with polyethylenimine (PheoA-PEI) with endosome escape activity and near-infrared imaging capability was prepared. A model antigen ovalbumin (OVA) was then complexed with PheoA-PEI to form PheoA-PEI/OVA nanoparticles (PheoA-PEI/OVA NPs) that are responsive to light...
March 28, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28294313/suppression-of-murine-tumour-growth-through-cd8-cytotoxic-t-lymphocytes-via-activated-dec-205-dendritic-cells-by-sequential-administration-of-%C3%AE-galactosylceramide-in-vivo
#18
Hideki Kogo, Masumi Shimizu, Yasuyuki Negishi, Eiji Uchida, Hidemi Takahashi
Cancer immunity is mediated through the effective priming and activation of tumour-specific class I MHC molecule-restricted CD8(+) cytotoxic T lymphocytes (CTLs). DEC-205(+) dendritic cells (DCs) can cross-present the epitope(s) of captured tumour antigens associated with class I MHC molecules alongside co-stimulatory molecules to prime and activate tumour-specific CD8(+) CTLs. Immunosuppressive tolerogenic DCs with reduced co-stimulatory molecules may be a cause of impaired CTL induction. Hepa1-6-1 cells were established from the mouse hepatoma cell line Hepa1-6; these cells grow continuously after subcutaneous implantation into syngeneic C57BL/6 (B6) mice and do not prime CD8(+) CTLs...
March 12, 2017: Immunology
https://www.readbyqxmd.com/read/28287107/dying-cells-actively-regulate-adaptive-immune-responses
#19
REVIEW
Nader Yatim, Sean Cullen, Matthew L Albert
Dying cells have an important role in the initiation of CD8(+) T cell-mediated immunity. The cross-presentation of antigens derived from dying cells enables dendritic cells to present exogenous tissue-restricted or tumour-restricted proteins on MHC class I molecules. Importantly, this pathway has been implicated in multiple autoimmune diseases and accounts for the priming of tumour antigen-specific T cells. Recent data have revealed that in addition to antigen, dying cells provide inflammatory and immunogenic signals that determine the efficiency of CD8(+) T cell cross-priming...
April 2017: Nature Reviews. Immunology
https://www.readbyqxmd.com/read/28277646/efficient-nanovaccine-delivery-in-cancer-immunotherapy
#20
Guizhi Zhu, Fuwu Zhang, Qianqian Ni, Gang Niu, Xiaoyuan Chen
Vaccines hold tremendous potential for cancer immunotherapy by treating the immune system. Subunit vaccines, including molecular adjuvants and cancer-associated antigens or cancer-specific neoantigens, can elicit potent antitumor immunity. However, subunit vaccines have shown limited clinical benefit in cancer patients, which is in part attributed to inefficient vaccine delivery. In this Perspective, we discuss vaccine delivery by synthetic nanoparticles or naturally derived nanoparticles for cancer immunotherapy...
March 28, 2017: ACS Nano
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